Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability o...Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.展开更多
The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating ...The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.展开更多
AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (D...AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.展开更多
Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these gene...Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these genes in common wheat. Here, we isolated a novel wheat WAK gene TaWAK5 from sharp eyespot disease-resistant wheat line CI12633,based on a differentially-expressed sequence identified by microarray analysis. The transcript abundance of TaWAK5 was rapidly increased following inoculation with the pathogen Rhizoctonia cerealis. TaWAK5 in resistant wheat lines was induced to higher levels than in susceptible lines at 7 days post inoculation with R. cerealis. The expression of TaWAK5 was also induced by treatments with exogenous salicylic acid, abscisic acid, and methyl jasmonate. The deduced TaWAK5 protein contained a signal peptide, two epidermal growth factor(EGF)-like repeats, a transmembrane domain, and a serine/threonine protein kinase catalytic domain. Subcellular localization analyses in onion epidermal cells indicated that the TaWAK5 protein was localized to the plasma membrane. Virus-induced gene silencing of TaWAK5 in CI12633 plants showed that the silencing of TaWAK5 did not obviously impair wheat resistance to R. cerealis, suggesting that TaWAK5 may be not the major gene in wheat defense response to R. cerealis, or that it is functionally redundant with other genes. This study paves the way for further research into WAK functions in wheat stress physiology.展开更多
In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated gr...In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells (BMNC)was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P<0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.展开更多
The membrane-phospholipid (MPL)injury of myocardial cells may play an important role in the development of heart failure.In present study, peripheral lymphocytes were used as a study model in which the protective and ...The membrane-phospholipid (MPL)injury of myocardial cells may play an important role in the development of heart failure.In present study, peripheral lymphocytes were used as a study model in which the protective and reparative effects of Captopril and Cocnzyme 10 (Coo10)on mitochondrial MPL injury were observed. 42 hospitalized patients with dilated cardiomyopathy(DCM),on conventional anti-heart-failure therapy, were divided into three groups at random,and Captopil (Capton),Neuquinone 10 (CoQ10) and placebo were added respectively.The A4PL localization was proceeded by modified Demer's tricomplex flocculation.After mean 75'5 days observation,in Captopril and CoQ10 groups, heart function was improved,with circulatory A1 decreased,the degree of mitochondrial proliferation of lymphocytes decreased and the mitochondrial MPL injury repaired in certain degree.The percentages of the lymphocytes with less than 5 mitochondria per lymphocyte increased [(60.0± 9.4)vs (72.0± 6. 8)% for Captopril;(55.0±8.9) vs (73.1 ± 9. 8)% for CoQ10, P<0. 001];the percentages of mitochondria with intact MPL localization increased [(59. 1 ± 8. 1 ) vs (72. 0± 9. 4)% for Captopril;(56.6±9.3) vs (73.8±9. 4)% for CoQ10 P< 0.001].But no significant changes were found in either the proliferation or MPL injury in the con trols. In conclusion,Captopril and CoQ10 have a beneficial effects on the protection and reparation of mitochondrial injury in patients with DCM.展开更多
The technique of supported liquid membranes was used to achieve the facilitated transport of Cr(III) ions, using tow amphiphilic carriers, the methyl cholate and resorcinarene. For prepared SLMs, toluene as organic ph...The technique of supported liquid membranes was used to achieve the facilitated transport of Cr(III) ions, using tow amphiphilic carriers, the methyl cholate and resorcinarene. For prepared SLMs, toluene as organic phase and film of polyvinylidene difluoride, as hydrophobic polymer support with 100 μm in thickness and 0.45 μm as the diameter of the pores. The macroscopic parameters (P and J0) on the transport of these ions were determined for different medium temperatures. For these different environments, the prepared SLMs were highly permeable and a clear evolution of these parameters was observed. The parameter J0 depended on the temperature according to the Arrhenius equation. The activation parameters, Ea, ΔH≠ and ΔS≠, for the transition state on the reaction of complex formation (ST) , were determined. To explain these results for this phenomenon, and achieve a better extraction of the substrate, a model based on the substrate complexation by the carrier and the diffusion of the formed complex (ST) was developed. The experimental results verify this model and determine the microscopic parameters (Kass and D*). These studies show that these parameters Kass and D* are specific to facilitated transport of Cr(III) ions by each of the carriers and they are changing significantly with temperature.展开更多
基金supported by fund from the National Natural Science Foundation of China(32172322)。
文摘Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.
基金Supported by the National Natural Science Foundation of China,No.82204755,and No.81960751the Guangxi Natural Science Foundation Youth Project,No.2023GXNSFBA026274+1 种基金the Guangxi University of Traditional Chinese Medicine School-level Project Youth Fund,No.2022QN008Faculty of Chinese Medicine Science Guangxi University of Chinese Medicine Research Project,No.2022MS008 and No.2022QJ001.
文摘The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.
基金National Natural Science Foundation of China,No.39770300,30070873the Overseas Chinese Affairs Office of the State Council Foundation,No.98-33
文摘AIM: To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim). METHODS: Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO. CONCLUSION: The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.
基金funded by the National Natural Science Foundation of China(31271799)the National "Key Sci-Tech" program,China(2013ZX08002-001-004)the China–Czech Government Science and Technology Cooperation Project(40–3 and LH12196)
文摘Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these genes in common wheat. Here, we isolated a novel wheat WAK gene TaWAK5 from sharp eyespot disease-resistant wheat line CI12633,based on a differentially-expressed sequence identified by microarray analysis. The transcript abundance of TaWAK5 was rapidly increased following inoculation with the pathogen Rhizoctonia cerealis. TaWAK5 in resistant wheat lines was induced to higher levels than in susceptible lines at 7 days post inoculation with R. cerealis. The expression of TaWAK5 was also induced by treatments with exogenous salicylic acid, abscisic acid, and methyl jasmonate. The deduced TaWAK5 protein contained a signal peptide, two epidermal growth factor(EGF)-like repeats, a transmembrane domain, and a serine/threonine protein kinase catalytic domain. Subcellular localization analyses in onion epidermal cells indicated that the TaWAK5 protein was localized to the plasma membrane. Virus-induced gene silencing of TaWAK5 in CI12633 plants showed that the silencing of TaWAK5 did not obviously impair wheat resistance to R. cerealis, suggesting that TaWAK5 may be not the major gene in wheat defense response to R. cerealis, or that it is functionally redundant with other genes. This study paves the way for further research into WAK functions in wheat stress physiology.
基金the National Natural Science Foundation of China (No. 81202839)the National Natural Science Foundation of China (No. 81774080)+1 种基金the “Taishan Scholar” Project Special Fundthe Study Abroad Funding by the Shandong health science and technology association and the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.
文摘In order to investigate the mechanism of mitochondrial membrane stabilization by Angelica sinensis polysaccharide (ASP) in murine aplastic anemia (AA).ICR mice were randomly divided into control, AA and ASP-treated groups. The AA group mice were treated with 60Coγand intraperitoneal injections of cyclophosphamide and chloramphenicol. The control animals were treated with lead shielding irradiation and saline injection. The treated AA mice were fed with ASP for 2 wk. Mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy, and the transmembrane potential of bone marrow-nucleated cells (BMNC)was examined by fluorescence spectrophotometry. The Cox and MDH contents of the medium were also studied in the three groups.The mitochondrial number and transmembrane potential of BMNC in the bone marrow decreased in the AA group as compared to the control group, but improved in the ASP-treated group as compared to the AA group. Complete mitochondrial cleavage in the ASP-treated group was significantly delayed (P<0.05) as compared to the AA group. We conclude that ASP might improve mitochondrial membrane stabilization, and suppress the downregulation of transmembrane potential and apoptosis of BMNC in AA.
文摘The membrane-phospholipid (MPL)injury of myocardial cells may play an important role in the development of heart failure.In present study, peripheral lymphocytes were used as a study model in which the protective and reparative effects of Captopril and Cocnzyme 10 (Coo10)on mitochondrial MPL injury were observed. 42 hospitalized patients with dilated cardiomyopathy(DCM),on conventional anti-heart-failure therapy, were divided into three groups at random,and Captopil (Capton),Neuquinone 10 (CoQ10) and placebo were added respectively.The A4PL localization was proceeded by modified Demer's tricomplex flocculation.After mean 75'5 days observation,in Captopril and CoQ10 groups, heart function was improved,with circulatory A1 decreased,the degree of mitochondrial proliferation of lymphocytes decreased and the mitochondrial MPL injury repaired in certain degree.The percentages of the lymphocytes with less than 5 mitochondria per lymphocyte increased [(60.0± 9.4)vs (72.0± 6. 8)% for Captopril;(55.0±8.9) vs (73.1 ± 9. 8)% for CoQ10, P<0. 001];the percentages of mitochondria with intact MPL localization increased [(59. 1 ± 8. 1 ) vs (72. 0± 9. 4)% for Captopril;(56.6±9.3) vs (73.8±9. 4)% for CoQ10 P< 0.001].But no significant changes were found in either the proliferation or MPL injury in the con trols. In conclusion,Captopril and CoQ10 have a beneficial effects on the protection and reparation of mitochondrial injury in patients with DCM.
基金All authors thank the Agence Universitaire de la Fran-cophonie(AUF)for financial support(PCSI 59113PS 014)Professor Jean-François Verchère from the University of Rouen(France)for his advice,fruitful dis-cussions,strong encouragement and exemplary coopera-tion.
文摘The technique of supported liquid membranes was used to achieve the facilitated transport of Cr(III) ions, using tow amphiphilic carriers, the methyl cholate and resorcinarene. For prepared SLMs, toluene as organic phase and film of polyvinylidene difluoride, as hydrophobic polymer support with 100 μm in thickness and 0.45 μm as the diameter of the pores. The macroscopic parameters (P and J0) on the transport of these ions were determined for different medium temperatures. For these different environments, the prepared SLMs were highly permeable and a clear evolution of these parameters was observed. The parameter J0 depended on the temperature according to the Arrhenius equation. The activation parameters, Ea, ΔH≠ and ΔS≠, for the transition state on the reaction of complex formation (ST) , were determined. To explain these results for this phenomenon, and achieve a better extraction of the substrate, a model based on the substrate complexation by the carrier and the diffusion of the formed complex (ST) was developed. The experimental results verify this model and determine the microscopic parameters (Kass and D*). These studies show that these parameters Kass and D* are specific to facilitated transport of Cr(III) ions by each of the carriers and they are changing significantly with temperature.
