The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulate...The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulates the supply of variable ATP demands in cells by“allosteric ATP-inhibition of CytOx.”This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx.The mechanism keeps mitochondrial membrane potentialΔΨm and reactive oxygen species(ROS)formation at low healthy values.Stress signals increase cytosolic calcium leading to Ca^2+-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATPinhibition and monomerization of CytOx.This is followed by increase ofΔΨm and formation of ROS.A hypothesis is presented suggesting a dynamic change of binding of NDUFA4,originally identified as a subunit of complex I,between monomeric CytOx(active state with highΔΨm,high ROS and low efficiency)and complex I(resting state with lowΔΨm,low ROS and high efficiency).展开更多
Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of ...Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.展开更多
The roles of NF-kappaB (NF-κB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were ...The roles of NF-kappaB (NF-κB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups: G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased (P〈0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups (P〈0.05). It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.展开更多
The extraction of cytochrome C was carried out by means of phase transfer technique with three different reverse micellar systems, i.e. , a CTAB micellar solution in n butyl alcohol chloroform(volume ratio 4...The extraction of cytochrome C was carried out by means of phase transfer technique with three different reverse micellar systems, i.e. , a CTAB micellar solution in n butyl alcohol chloroform(volume ratio 4∶1), an AOT micellar solution in isooctane and a SDSS D 2EHPA micellar solution in isooctane. The extraction mechanisms were studied. The results show that the extraction mechanisms for the same proteins with different types of reverse micellar systems can be distinct. The extraction of cytochrome C with CTAB and SDSS D 2EHPA reverse micellar systems are carried out according to the mechanism of electrostatic interaction. However, in the extraction of cytochrome C with the AOT reverse micellar system, the electrostatic interaction between the protein and the surfactant is not important.展开更多
Noncovalent interactions between ligands and targeting proteins are essential for understanding molecular mechanisms of proteins.In this work,we investigated the interaction of Cytochrome c(Cyt c)with maltoligosacchar...Noncovalent interactions between ligands and targeting proteins are essential for understanding molecular mechanisms of proteins.In this work,we investigated the interaction of Cytochrome c(Cyt c)with maltoligosaccharides,namely maltose(Mal Ⅱ),maltotriose(Mal Ⅲ),maltotetraose(Mal Ⅳ),maltopentaose(Mal Ⅴ),maltohexaose(Mal Ⅵ)and maltoheptaose(Mal Ⅶ).Using electrospray ionization mass spetrometry(ESI-MS)assay,the 1:1 and 1:2 complexes formed by Cyt c with maltoligosaccharide ligand were observed.The corresponding association constants were calculated according to the deconvoluted spectra.The order of the relative binding affinities of the selected oligosaccharides with Cyt c were as MalⅢ>MalⅣ>MalⅡ>MalⅤ>MalⅥ>MalⅦ.The results indicated that the stability of noncovalent protein complexes was intimately correlated to the molecular structure of bound ligand.The relevant functional groups that could form H-bonds,electrostatic or hydrophobic forces with protein’s amino residues played an important role for the stability of protein complexes.In addition,the steric structure of ligand was also critical for an appropriate interaction with the binding pocket of proteins.展开更多
In this study, a lipid membrane was fabricated by fusing cardiolipin-phosphatidylcholine(CL_PC, 1:4) vesicles onto a hydrophobic surface of 1-dodecanethiol(DT) preadsorbed on a nanostructured gold film. By changi...In this study, a lipid membrane was fabricated by fusing cardiolipin-phosphatidylcholine(CL_PC, 1:4) vesicles onto a hydrophobic surface of 1-dodecanethiol(DT) preadsorbed on a nanostructured gold film. By changing the concentration of the DT adsorption solution, we constructed a series of CL PC-DT bilayers with different hydrophobicity to study the effects of lipid membrane characteristics on the adsorption conformation of cytochrome c(Cyt c). Electrochemical analysis showed that the formal potential is 0.24 V for Cyt c-CL_PC-DT(10), 0.2 V for Cyt c-CL_PC-DT(20), and 0.16 V for Cyt c-CL_PC-DT(40) — a gradual positive shift with the decreasing DT concentration — relative to the potential of native cyt c(0.02 V). Potential-induced surface-enhanced infrared adsorption difference spectroscopy revealed that the gradual positive shift of the formal potential of CL-bound cyt c is determined by the environment with the gradually lowered dielectric constant for the heme cofactor in CL-bound cyt c(Fe^3+).展开更多
The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria....The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria. Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time. Further analysis revealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one disappeared mutational site at 1 month after cerebral ischemia. Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the DatholoQical Process of ischemic brain iniurv.展开更多
With 1-Pymnebutyric acid (PBA) and multiwalled carbon nanotubes (MWNTs), glassy carbon electrode modified was successfully prepared. In phosphate buffer solution (pH 7,0), the direct electrochemistry of cytochro...With 1-Pymnebutyric acid (PBA) and multiwalled carbon nanotubes (MWNTs), glassy carbon electrode modified was successfully prepared. In phosphate buffer solution (pH 7,0), the direct electrochemistry of cytochrome C (Cyt C) was realized. In the cyclic voltammetry experiment two pairs of redox peaks ofCyt C were observed at 0.018 V and -0.314 V (vs. SCE), respectively. The redox reaction at 0.018 V was diffusion controlled, while the redox reaction at -0.314 V was adsorption controlled.展开更多
Quartz crystal microbalance(QCM) and cyclic voltammetry(CV) were used to characterize the monolayer of cytochrome c(Cyt c),which was adsorbed on gold film modified with alkanethiol mixed monolayer.A direct compa...Quartz crystal microbalance(QCM) and cyclic voltammetry(CV) were used to characterize the monolayer of cytochrome c(Cyt c),which was adsorbed on gold film modified with alkanethiol mixed monolayer.A direct comparison of protein surface coverages calculated from QCM and cyclic voltammetric measurements illustrates that the ratio of the electroactive Cyt c to the total surface-confined Cyt c is 34%,which suggests that the orientation is a main factor affecting the electroactivity of Cyt c.Moreover,surface plasmon resonance(SPR) measurement combined with CV "in situ" was used to investigate the conformational change of Cyt c in the redox process.Besides,Au nanoparticles(Au NPs) were adsorbed on the surface of Cyt c.The result indicates that Au NPs promote electron transfer between Cyt c and the gold electrode,and SPR result suggests Au NPs enhance SPR signal.展开更多
Objective: To study the effect of pioglitazone on mitochondrial Ca2+ and cytochrome c (cyt c) in early diabetic rats, and to explore its mechanism of protecting kidney. Methods: 72 DM rats were randomly divided into n...Objective: To study the effect of pioglitazone on mitochondrial Ca2+ and cytochrome c (cyt c) in early diabetic rats, and to explore its mechanism of protecting kidney. Methods: 72 DM rats were randomly divided into negative control group (NC group), negative control+ pioglitazone intervention group (NCP group), diabetes group (DM group) and diabetes +pioglitazone intervention group (DMP group). In NCP and DMP groups, pioglitazone was administered to the stomach, blood glucose, renal mass index, 24-h urine protein, glomerular morphologic indice, glomerular base-membrane thickness and other indexes were measured, and the contents of Ca2+ and Cyt C in renal tissue were measured. Results: (1) the renal metabolism index, glomerular morphologic indice, glomerular base-membrane thickness of DM group was significantly higher than that of NC group (P < 0.01). The renal metabolism index, glomerular morphologic indice, glomerular base-membrane thickness of DMP group was significantly lower than that of DM group, the difference between the two groups was significant(P<0.05). (2) in DM group, mitochondrial Ca2+ and cytoplasmic cytc were higher than those in NC group, while mitochondrial cytc was lower than that in control group. There was significant difference between the two groups (P < 0.05). In DMP group, mitochondrial Ca2+ and cytoplasmic cytc were lower than those in DM group, while mitochondrial cytc was higher than that in control group. There was significant difference between the two groups (P <0.05). Conclusion: Pioglitazone treatment can reduce the release of mitochondrial cytochrome C and maintain mitochondrial calcium homeostasis.展开更多
BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Wher...BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Whereas inosine can inhibit neuronal apoptosis which is similar to bcl-2. OBJECTIVE: To observe the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemia/reperfusion, and analyze the pathway of its neuroprotective effect. DESIGN: A randomised controlled animal trial. SETTINGS: Department of Neurology, Rongcheng Second People's Hospital; Department of Neurology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: Sixty-eight rats, weighing 230-280 g and clean grade, were used. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and cytochrome C mRNA in situ hybridization kits and DAB staining kit were purchased from Wuhan Boster Biological Co., Ltd.; Inosine injection [200 mg (2 mL) each] from Qingdao First Pharmaceutical Factory. METHODS: The experiment was accomplished in the animal experimental center in Tongji Medical College of Huazhong University of Science and Technology from December 2003 to June 2005. ① Sixty-four rats were made into focal ischemia by middle cerebral artery occlusion (MCAO) with a nylon monofilament suture. The successfully induced rats were assigned to inosine group (n =32) and model group (n =32) at random. Rats in the inosine group were intraperitoneally administrated with inosine in dose of 100 mg/kg preoperatively, twice a day, 7 days in all. The rats in the control group were injected with the same dose of saline solution by the similar way preoperatively. Each group was randomized into ischemia /reperfusion 2, 6, 12, 24 hours, 2, 3, 7 and 14 days subgroups consisted of 4 rats. The other 4 rats were taken as the sham-operated group, the rats were given the same treatment except for not introduced the filament into the external carotid artery stump, and brain tissue was removed at 2 hours of reperfusion. ② In situ hybridization was performed to examine the expression of cytochrome C mRNA while TUNEL staining was made to characterize apoptosis. ③ The t test was used to compare the difference of measurement data. MAIN OUTCOME MEASURES: ① Neuronal apoptosis in the different regions of the ischemic brain tissue; ② Expression of cytochrome C mRNA in the different regions at different time points after MCAO. RESULTS: All the 68 rats were involved in the analysis of results. ① Neuronal apoptosis: A small number of TUNEL-positive cells were detected in the sham-operated brain and non-ischemic brain. The number of apoptotic cells in the ischemic cortex peaked at 24 hours of reperfusion [(72.00±1.98) cells] and that in the striatum peaked at 2 days [(94.75±3.57) cells], then decreased to the level of sham-operated group at 14 days. Inosine could reduce apoptotic cells from 12 hours to 7 days of reperfusion as compared with the model group (t =6.19-26.67, P < 0.01). ② Cytochrome C mRNA expression: There was weak expression of cytochrome C mRNA in both sham-operated brain and contralateral brain. Cytochrome C was detected at 2 hours of reperfusion in ischemic brain [(25.75±3.50), (39.75±2.49) cells], and strongly increased to a peak at 12 hours and 24 hours of reperfusion in cortex and striatum [(122.50±6.69), (119.25±5.12) cells], respectively. Furthermore, inosine could significantly decrease cytochrome C expression in cortex at 12 hours to 14 days of reperfusion after ischemic reperfusion and that in striatum at 12 hours to 3 days (t =8.67-43.26, P < 0.01). CONCLUSION: Inosine can exert a neuroprotective effect by inhibiting apoptosis and cytochrome C mRNA expression.展开更多
It was found for the first time that the compounds with only one functional group, such as pyridine, can show the promotion effect for the electrochemical reaction of cytochrome C at gold electrodes.
Objective To construct Cox7a2 fluorescent vector and study its effect on cytochrome C oxidase ( COX) activity in mouse Sertoli cell line TM4. Methods The coding region of CoxTa2 was amplified from mouse Sertoli cell l...Objective To construct Cox7a2 fluorescent vector and study its effect on cytochrome C oxidase ( COX) activity in mouse Sertoli cell line TM4. Methods The coding region of CoxTa2 was amplified from mouse Sertoli cell line TM4 by RT-PCR. PCR product was展开更多
Most nanozyme research is limited to oxidase and peroxidase.Here,we reported the N,P,or S doped carbon nanotubes(CNTs)for enzyme mimics of nicotinamide adenine dinucleotide(NADH)oxidase and cytochrome c(Cyt c)reductas...Most nanozyme research is limited to oxidase and peroxidase.Here,we reported the N,P,or S doped carbon nanotubes(CNTs)for enzyme mimics of nicotinamide adenine dinucleotide(NADH)oxidase and cytochrome c(Cyt c)reductase.Through the doping of N element,the NADH oxidase-like activity of CNTs is highly improved,the maximum initial velocity for N doped CNT(N-CNT)is increased by 4.28 times compared to that before the modification.Through the analysis of NADH oxidation products,we found that biologically active NAD+was produced,the oxygen was selectively reduced to water or hydrogen peroxide,which is consistent with natural NADH oxidase.Furthermore,we found for the first time that carbon nanotubes can promote the transfer of electrons from NADH to Cyt c,thereby can mimic the properties of Cyt c reductase.展开更多
Objective: To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods: The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment...Objective: To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods: The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method. Results: Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar. Conclusion: The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.展开更多
As a result of the endosymbiotic gene transfer, the majority of proteins of mitochondria and chloroplasts is encoded in the nucleus and synthesized in the cytosol as precursor molecules carrying N-terminal transit pep...As a result of the endosymbiotic gene transfer, the majority of proteins of mitochondria and chloroplasts is encoded in the nucleus and synthesized in the cytosol as precursor molecules carrying N-terminal transit peptides for the transport into the respective target organelle. In most instances, transport takes place into either mitochondria or chloroplasts, although a few examples of dual targeting into both organelles have been described. Here, we show by a combination of three different experimental strategies that also cytochrome c1 of potato, a component of the respiratory electron transport chain, is imported not only into mitochondria, but also into plastids. In organello import experiments with isolated mitochondria and chloroplasts, which were analyzed in both single and mixed organelte assays, demonstrate that the processing products accumulating after import within the two endosymbiotic organelles are different in size. Dual targeting of cytochrome c1 is observed also in vivo, after biolistic transformation of leaf epidermal cells with suitable reporter constructions. Finally, Western analyses employing cytochrome c1-specific antiserum provide evidence that the protein accumulates in significant amounts in mitochondria and chloroplasts of both pea and spinach. The possible consequences of our findings on the relevance of the dual targeting phenomenon are discussed.展开更多
Monodisperse TiO2 nanoparticles and urchin-like hierarchical TiO2 nanospheres assembled with ultrathin quantum nanowires(about 2 nm)have been synthesized by a simple template-free wet chemical method.The morphology,st...Monodisperse TiO2 nanoparticles and urchin-like hierarchical TiO2 nanospheres assembled with ultrathin quantum nanowires(about 2 nm)have been synthesized by a simple template-free wet chemical method.The morphology,structure,and crystallinity of the TiO2 nanomaterials were investigated by field emission scanning electron microscopy(FESEM),X-ray diffraction(XRD),and high resolution transmission electron microscopy(HRTEM).Electrochemical measurements with the hierarchically nanostructured TiO2 nanospheres as an electrode showed much better reversibility for direct electrochemistry of cytochrome c(cyt c)and much higher sensitivity than for an electrode composed of the monodisperse TiO2 nanoparticles.The excellent performance of the hierarchical TiO2 nanospheres may result from a quantum size effect,and their favorable nanostructure(with the presence of an abundance of both uniform macropores and mesopores),excellent structural stability and high specific surface area.The relative ionic strength had significant effect on the direct electrochemistry.Very high ionic strengths relative to cyt c concentration(I/c)induced a conformational change of cyt c on the nanostructure-coated electrode,from the native state to a partially unfolded one in 25 mmol/L phosphate buffer solution(pH 6.8).展开更多
Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentrat...Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight (SELDI-TOF) mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography (HPLC).Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs).Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11605.4) from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.展开更多
The secondary structures of native cytochrome c(cyt c)in both solid and solution states and four platinum modified cyt c derivatives in solution were determined by means of Fourier transform infrared spectroscopy.It w...The secondary structures of native cytochrome c(cyt c)in both solid and solution states and four platinum modified cyt c derivatives in solution were determined by means of Fourier transform infrared spectroscopy.It was found that the secondary structure of cyt c in solid state is similar to that in the solution.In the cases of platinum modified cyt c derivatives,when the binding sites of platinum complex are on or near the surface of the protein,its secondary structure is similar to that of native cyt c.However,when the platinum complex binds to Met 80 ligand and causes the replacement of the second axial ligand by non native Lys 79 ligand or H 2O supplied by solvent,there is a significant difference between the structures of low or high spin state cyt c derivatives and that of native cyt c.The results suggest that axial ligand Met 80 residue plays an important role in stabilizing the secondary structure of cyt c.展开更多
Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism o...Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.Methods:In this study,the effects of TRAP1 and cytochrome c oxidase subunit Ⅱ(COXⅡ)on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.Results:Hypoxia induced cardiomyocyte apoptosis,and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia.Conversely,TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes.Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXⅡ overexpression,whereas COXⅡ knockdown reduced the antiapoptotic function induced by TRAP1 overexpression.Additionally,changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm,as well as reactive oxygen species production,were found to be correlated with the changes in apoptosis.Conclusions:The current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXⅡ,in which reactive oxygen species presents as an important component.展开更多
文摘The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulates the supply of variable ATP demands in cells by“allosteric ATP-inhibition of CytOx.”This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx.The mechanism keeps mitochondrial membrane potentialΔΨm and reactive oxygen species(ROS)formation at low healthy values.Stress signals increase cytosolic calcium leading to Ca^2+-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATPinhibition and monomerization of CytOx.This is followed by increase ofΔΨm and formation of ROS.A hypothesis is presented suggesting a dynamic change of binding of NDUFA4,originally identified as a subunit of complex I,between monomeric CytOx(active state with highΔΨm,high ROS and low efficiency)and complex I(resting state with lowΔΨm,low ROS and high efficiency).
文摘Objective To investigate the possible effect of artesunate (ART) on schistosome thioredoxin glutathione reductase (TGR) and cytochrome c peroxidase (CcP) in Schistosoma mansoni-infected mice. Methods A total of 200 laboratory bred male Swiss albino mice were divided into 4 groups (50 mice in each group). Group I: infected untreated group (Control group) received a vehicle of 1% sodium carbonyl methylcellulose (CMC-Na); Group II: infected then treated with artesunate; Group III infected then treated with praziquantel, and group IV: infected then treated with artesunate then praziquantel. Adult S. mansoni worms were collected by Animal Perfusion Method, tissue egg counted, TGR, and CcP mRNA Expression were estimated of in $. mansoni adult worms by semi-quantitative rt-PCR. Results Semi-quantitative rt-PCR values revealed that treatment with artesunate caused significant decrease in expression of schistosome TGR and CcP in comparison to the untreated group. In contrast, the treatment with praziquantel did not cause significant change in expression of these genes. The results showed more reduction in total worm and female worm count in combined ART-PZQ treated group than in monotherapy treated groups by either ART or PZO, Moreover, complete disappearance (100%) of tissue eggs was recorded in ART-PZQ treated group with a respective reduction rate of 95.9% and 68.4% in ART- and PZQ-treated groups. Conclusion The current study elucidated for the first time that anti-schistosomal mechanisms of artesunate is mediated via reduction in expression of schistosome TGR and CcP. Linking these findings, addition of artesunate to praziquantel could achieve complete cure outcome in treatment of schistosomiasis.
基金supported by the grants from GuangxiSciences foundation(No.0542083)Chunhui Program of theNational Education Ministry(2003)National NaturalSciences Foundation(No.30860116)
文摘The roles of NF-kappaB (NF-κB) expression, Bax activity and cytochrome C (Cyt C) release, apoptosis of islet cells induced by high concentration glucose were explored in vitro. Pancreatic islet cells, which were isolated from Kunming mice, were cultured with different concentrations of glucose in DMEM, and divided into the following groups: G1, G2, G3, G4, G5, and G6 groups, corresponding to the glucose concentrations of 5.6, 7.8, 11.1, 16.7, 22.5, and 27.6 mmol/L, respectively. After culture for 120 h, insulin secretion was evaluated by radioimmunoassay, and the NF-rd3 expression was detected by immunocytochemistry. Bax activity and Cyt C release were measured by immunofluorescence, and apoptosis was examined by Hoechst33342 assay. The results showed that in GI, G2 and G3 groups, insulin secretion was enhanced with the increase of glucose concentration, and the NF-κB expression was also increased (P〈0.05), but Bax activity, Cyt C release and apoptosis rate showed no significant difference among them. However, in G4, G5, and G6 groups, apoptosis rate of islet cells, NF-rd3 expression, Bax activity, and Cyt C release were all significantly increased, and insulin secretion was impaired as compared with G1, G2, and G3 groups (P〈0.05). It was concluded that the exposure of islet cells to high glucose could induce islet cells apoptosis as well as impaired insulin secretion. The NF-κB signaling pathway and mitochondria pathway in islet cells might play some roles in the progressive loss of islet cells in diabetes. The inhibition of the NF-κB expression could be an effective strategy for protecting pancreatic islet cells.
文摘The extraction of cytochrome C was carried out by means of phase transfer technique with three different reverse micellar systems, i.e. , a CTAB micellar solution in n butyl alcohol chloroform(volume ratio 4∶1), an AOT micellar solution in isooctane and a SDSS D 2EHPA micellar solution in isooctane. The extraction mechanisms were studied. The results show that the extraction mechanisms for the same proteins with different types of reverse micellar systems can be distinct. The extraction of cytochrome C with CTAB and SDSS D 2EHPA reverse micellar systems are carried out according to the mechanism of electrostatic interaction. However, in the extraction of cytochrome C with the AOT reverse micellar system, the electrostatic interaction between the protein and the surfactant is not important.
基金supported by the National Natural Science Foundation of China(Grant No.21675176)the Natural Science Foundation of Hubei Province(Grant No.2014CFA025)the Preferred Research Foundation for the Returned Overseas Scholars from Ministry of Human Resources and Social Security of the People’s Republic of China(Grant No.BZY14036)for financial supports.
文摘Noncovalent interactions between ligands and targeting proteins are essential for understanding molecular mechanisms of proteins.In this work,we investigated the interaction of Cytochrome c(Cyt c)with maltoligosaccharides,namely maltose(Mal Ⅱ),maltotriose(Mal Ⅲ),maltotetraose(Mal Ⅳ),maltopentaose(Mal Ⅴ),maltohexaose(Mal Ⅵ)and maltoheptaose(Mal Ⅶ).Using electrospray ionization mass spetrometry(ESI-MS)assay,the 1:1 and 1:2 complexes formed by Cyt c with maltoligosaccharide ligand were observed.The corresponding association constants were calculated according to the deconvoluted spectra.The order of the relative binding affinities of the selected oligosaccharides with Cyt c were as MalⅢ>MalⅣ>MalⅡ>MalⅤ>MalⅥ>MalⅦ.The results indicated that the stability of noncovalent protein complexes was intimately correlated to the molecular structure of bound ligand.The relevant functional groups that could form H-bonds,electrostatic or hydrophobic forces with protein’s amino residues played an important role for the stability of protein complexes.In addition,the steric structure of ligand was also critical for an appropriate interaction with the binding pocket of proteins.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.9122711421322510+4 种基金and 21105097)the China Postdoctoral Science Foundation(Grant No.2013M530998)the Natural Science Foundation of Jilin ProvinceChina(Grant No.201215092)the President Funds of the Chinese Academy of Sciences
文摘In this study, a lipid membrane was fabricated by fusing cardiolipin-phosphatidylcholine(CL_PC, 1:4) vesicles onto a hydrophobic surface of 1-dodecanethiol(DT) preadsorbed on a nanostructured gold film. By changing the concentration of the DT adsorption solution, we constructed a series of CL PC-DT bilayers with different hydrophobicity to study the effects of lipid membrane characteristics on the adsorption conformation of cytochrome c(Cyt c). Electrochemical analysis showed that the formal potential is 0.24 V for Cyt c-CL_PC-DT(10), 0.2 V for Cyt c-CL_PC-DT(20), and 0.16 V for Cyt c-CL_PC-DT(40) — a gradual positive shift with the decreasing DT concentration — relative to the potential of native cyt c(0.02 V). Potential-induced surface-enhanced infrared adsorption difference spectroscopy revealed that the gradual positive shift of the formal potential of CL-bound cyt c is determined by the environment with the gradually lowered dielectric constant for the heme cofactor in CL-bound cyt c(Fe^3+).
基金the International Cooperation Program of Science and Technology Department of Jilin Province, No. 20100751
文摘The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria. Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time. Further analysis revealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one disappeared mutational site at 1 month after cerebral ischemia. Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the DatholoQical Process of ischemic brain iniurv.
基金This project was jointly supported by the National Natural Science Foundation of China(No.50134020)by the Foundation of Doctoral Prograrms of the Ministry of Education of China(No.20010001028).
文摘With 1-Pymnebutyric acid (PBA) and multiwalled carbon nanotubes (MWNTs), glassy carbon electrode modified was successfully prepared. In phosphate buffer solution (pH 7,0), the direct electrochemistry of cytochrome C (Cyt C) was realized. In the cyclic voltammetry experiment two pairs of redox peaks ofCyt C were observed at 0.018 V and -0.314 V (vs. SCE), respectively. The redox reaction at 0.018 V was diffusion controlled, while the redox reaction at -0.314 V was adsorption controlled.
基金Supported by the National Natural Science Foundation of China(Nos.20833005,20873116,60936003 and 21021002)the Fund of the State Key Laboratory of Superamolecular Structure and Materials,Jilin University,China(No.200910)
文摘Quartz crystal microbalance(QCM) and cyclic voltammetry(CV) were used to characterize the monolayer of cytochrome c(Cyt c),which was adsorbed on gold film modified with alkanethiol mixed monolayer.A direct comparison of protein surface coverages calculated from QCM and cyclic voltammetric measurements illustrates that the ratio of the electroactive Cyt c to the total surface-confined Cyt c is 34%,which suggests that the orientation is a main factor affecting the electroactivity of Cyt c.Moreover,surface plasmon resonance(SPR) measurement combined with CV "in situ" was used to investigate the conformational change of Cyt c in the redox process.Besides,Au nanoparticles(Au NPs) were adsorbed on the surface of Cyt c.The result indicates that Au NPs promote electron transfer between Cyt c and the gold electrode,and SPR result suggests Au NPs enhance SPR signal.
基金Key medical and health project of nanjing military region
文摘Objective: To study the effect of pioglitazone on mitochondrial Ca2+ and cytochrome c (cyt c) in early diabetic rats, and to explore its mechanism of protecting kidney. Methods: 72 DM rats were randomly divided into negative control group (NC group), negative control+ pioglitazone intervention group (NCP group), diabetes group (DM group) and diabetes +pioglitazone intervention group (DMP group). In NCP and DMP groups, pioglitazone was administered to the stomach, blood glucose, renal mass index, 24-h urine protein, glomerular morphologic indice, glomerular base-membrane thickness and other indexes were measured, and the contents of Ca2+ and Cyt C in renal tissue were measured. Results: (1) the renal metabolism index, glomerular morphologic indice, glomerular base-membrane thickness of DM group was significantly higher than that of NC group (P < 0.01). The renal metabolism index, glomerular morphologic indice, glomerular base-membrane thickness of DMP group was significantly lower than that of DM group, the difference between the two groups was significant(P<0.05). (2) in DM group, mitochondrial Ca2+ and cytoplasmic cytc were higher than those in NC group, while mitochondrial cytc was lower than that in control group. There was significant difference between the two groups (P < 0.05). In DMP group, mitochondrial Ca2+ and cytoplasmic cytc were lower than those in DM group, while mitochondrial cytc was higher than that in control group. There was significant difference between the two groups (P <0.05). Conclusion: Pioglitazone treatment can reduce the release of mitochondrial cytochrome C and maintain mitochondrial calcium homeostasis.
基金the Natural Science Fund of Shandong Province, No.Y2001C04
文摘BACKGROUND: It has been demonstrated that adenosine can induce glial cell to release cytochrome C, enhance expression of apoptotic gene bax, inhibit anti-apoptotic gene bcl-2, and activate caspase-3 to apoptosis; Whereas inosine can inhibit neuronal apoptosis which is similar to bcl-2. OBJECTIVE: To observe the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemia/reperfusion, and analyze the pathway of its neuroprotective effect. DESIGN: A randomised controlled animal trial. SETTINGS: Department of Neurology, Rongcheng Second People's Hospital; Department of Neurology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: Sixty-eight rats, weighing 230-280 g and clean grade, were used. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and cytochrome C mRNA in situ hybridization kits and DAB staining kit were purchased from Wuhan Boster Biological Co., Ltd.; Inosine injection [200 mg (2 mL) each] from Qingdao First Pharmaceutical Factory. METHODS: The experiment was accomplished in the animal experimental center in Tongji Medical College of Huazhong University of Science and Technology from December 2003 to June 2005. ① Sixty-four rats were made into focal ischemia by middle cerebral artery occlusion (MCAO) with a nylon monofilament suture. The successfully induced rats were assigned to inosine group (n =32) and model group (n =32) at random. Rats in the inosine group were intraperitoneally administrated with inosine in dose of 100 mg/kg preoperatively, twice a day, 7 days in all. The rats in the control group were injected with the same dose of saline solution by the similar way preoperatively. Each group was randomized into ischemia /reperfusion 2, 6, 12, 24 hours, 2, 3, 7 and 14 days subgroups consisted of 4 rats. The other 4 rats were taken as the sham-operated group, the rats were given the same treatment except for not introduced the filament into the external carotid artery stump, and brain tissue was removed at 2 hours of reperfusion. ② In situ hybridization was performed to examine the expression of cytochrome C mRNA while TUNEL staining was made to characterize apoptosis. ③ The t test was used to compare the difference of measurement data. MAIN OUTCOME MEASURES: ① Neuronal apoptosis in the different regions of the ischemic brain tissue; ② Expression of cytochrome C mRNA in the different regions at different time points after MCAO. RESULTS: All the 68 rats were involved in the analysis of results. ① Neuronal apoptosis: A small number of TUNEL-positive cells were detected in the sham-operated brain and non-ischemic brain. The number of apoptotic cells in the ischemic cortex peaked at 24 hours of reperfusion [(72.00±1.98) cells] and that in the striatum peaked at 2 days [(94.75±3.57) cells], then decreased to the level of sham-operated group at 14 days. Inosine could reduce apoptotic cells from 12 hours to 7 days of reperfusion as compared with the model group (t =6.19-26.67, P < 0.01). ② Cytochrome C mRNA expression: There was weak expression of cytochrome C mRNA in both sham-operated brain and contralateral brain. Cytochrome C was detected at 2 hours of reperfusion in ischemic brain [(25.75±3.50), (39.75±2.49) cells], and strongly increased to a peak at 12 hours and 24 hours of reperfusion in cortex and striatum [(122.50±6.69), (119.25±5.12) cells], respectively. Furthermore, inosine could significantly decrease cytochrome C expression in cortex at 12 hours to 14 days of reperfusion after ischemic reperfusion and that in striatum at 12 hours to 3 days (t =8.67-43.26, P < 0.01). CONCLUSION: Inosine can exert a neuroprotective effect by inhibiting apoptosis and cytochrome C mRNA expression.
基金The project is supported by National Natural Science Foundation of China
文摘It was found for the first time that the compounds with only one functional group, such as pyridine, can show the promotion effect for the electrochemical reaction of cytochrome C at gold electrodes.
文摘Objective To construct Cox7a2 fluorescent vector and study its effect on cytochrome C oxidase ( COX) activity in mouse Sertoli cell line TM4. Methods The coding region of CoxTa2 was amplified from mouse Sertoli cell line TM4 by RT-PCR. PCR product was
基金the National Key Research and Development Program of China(No.2019YFA0709202)Natural Science Foundation of Jilin Province(No.20220101055JC)+1 种基金the International Cooperation Project of Jilin Scientific and Technological Development Program(No.20190701059GH)the National Natural Science Foundation of China(No.31301177).
文摘Most nanozyme research is limited to oxidase and peroxidase.Here,we reported the N,P,or S doped carbon nanotubes(CNTs)for enzyme mimics of nicotinamide adenine dinucleotide(NADH)oxidase and cytochrome c(Cyt c)reductase.Through the doping of N element,the NADH oxidase-like activity of CNTs is highly improved,the maximum initial velocity for N doped CNT(N-CNT)is increased by 4.28 times compared to that before the modification.Through the analysis of NADH oxidation products,we found that biologically active NAD+was produced,the oxygen was selectively reduced to water or hydrogen peroxide,which is consistent with natural NADH oxidase.Furthermore,we found for the first time that carbon nanotubes can promote the transfer of electrons from NADH to Cyt c,thereby can mimic the properties of Cyt c reductase.
文摘Objective: To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods: The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method. Results: Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar. Conclusion: The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.
文摘As a result of the endosymbiotic gene transfer, the majority of proteins of mitochondria and chloroplasts is encoded in the nucleus and synthesized in the cytosol as precursor molecules carrying N-terminal transit peptides for the transport into the respective target organelle. In most instances, transport takes place into either mitochondria or chloroplasts, although a few examples of dual targeting into both organelles have been described. Here, we show by a combination of three different experimental strategies that also cytochrome c1 of potato, a component of the respiratory electron transport chain, is imported not only into mitochondria, but also into plastids. In organello import experiments with isolated mitochondria and chloroplasts, which were analyzed in both single and mixed organelte assays, demonstrate that the processing products accumulating after import within the two endosymbiotic organelles are different in size. Dual targeting of cytochrome c1 is observed also in vivo, after biolistic transformation of leaf epidermal cells with suitable reporter constructions. Finally, Western analyses employing cytochrome c1-specific antiserum provide evidence that the protein accumulates in significant amounts in mitochondria and chloroplasts of both pea and spinach. The possible consequences of our findings on the relevance of the dual targeting phenomenon are discussed.
基金This work was supported by the National Basic Research Program of China(No.2010CB934700)the National Natural Science Foundation of China(Nos.20973019,50902007,and 50725208).
文摘Monodisperse TiO2 nanoparticles and urchin-like hierarchical TiO2 nanospheres assembled with ultrathin quantum nanowires(about 2 nm)have been synthesized by a simple template-free wet chemical method.The morphology,structure,and crystallinity of the TiO2 nanomaterials were investigated by field emission scanning electron microscopy(FESEM),X-ray diffraction(XRD),and high resolution transmission electron microscopy(HRTEM).Electrochemical measurements with the hierarchically nanostructured TiO2 nanospheres as an electrode showed much better reversibility for direct electrochemistry of cytochrome c(cyt c)and much higher sensitivity than for an electrode composed of the monodisperse TiO2 nanoparticles.The excellent performance of the hierarchical TiO2 nanospheres may result from a quantum size effect,and their favorable nanostructure(with the presence of an abundance of both uniform macropores and mesopores),excellent structural stability and high specific surface area.The relative ionic strength had significant effect on the direct electrochemistry.Very high ionic strengths relative to cyt c concentration(I/c)induced a conformational change of cyt c on the nanostructure-coated electrode,from the native state to a partially unfolded one in 25 mmol/L phosphate buffer solution(pH 6.8).
文摘Background Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight (SELDI-TOF) mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography (HPLC).Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs).Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11605.4) from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.
文摘The secondary structures of native cytochrome c(cyt c)in both solid and solution states and four platinum modified cyt c derivatives in solution were determined by means of Fourier transform infrared spectroscopy.It was found that the secondary structure of cyt c in solid state is similar to that in the solution.In the cases of platinum modified cyt c derivatives,when the binding sites of platinum complex are on or near the surface of the protein,its secondary structure is similar to that of native cyt c.However,when the platinum complex binds to Met 80 ligand and causes the replacement of the second axial ligand by non native Lys 79 ligand or H 2O supplied by solvent,there is a significant difference between the structures of low or high spin state cyt c derivatives and that of native cyt c.The results suggest that axial ligand Met 80 residue plays an important role in stabilizing the secondary structure of cyt c.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant No:81101426,81571898).
文摘Background:Tumor necrosis factor receptor-associated protein 1(TRAP1)plays a protective effect in hypoxic cardiomyocytes,but the precise mechanisms are not well clarified.The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.Methods:In this study,the effects of TRAP1 and cytochrome c oxidase subunit Ⅱ(COXⅡ)on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.Results:Hypoxia induced cardiomyocyte apoptosis,and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia.Conversely,TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes.Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXⅡ overexpression,whereas COXⅡ knockdown reduced the antiapoptotic function induced by TRAP1 overexpression.Additionally,changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm,as well as reactive oxygen species production,were found to be correlated with the changes in apoptosis.Conclusions:The current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXⅡ,in which reactive oxygen species presents as an important component.