Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and...Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte hypertrophy.Methods:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass spectrometry.Cardiomyocytes were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 h.Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated.Subsequently,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying mechanism.Results:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene expression.Moreover,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes.Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col expression.Conclusion:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.展开更多
Diethyl flavon-7-yl phosphate was synthesized by modified Atheron-Todd reaction. The result of ESI shows that the phosphated flavonoids possess stronger binding affinities toward proteins such as myoglobin, insulin an...Diethyl flavon-7-yl phosphate was synthesized by modified Atheron-Todd reaction. The result of ESI shows that the phosphated flavonoids possess stronger binding affinities toward proteins such as myoglobin, insulin and lysozyme and are easier to form the non-covalent complexes with them.展开更多
The dynamic distribution of phosphorylated Histone H3 on Ser10 (phospho-H3) in cells was investigated to determineits function during mitosis. Human breast adenocarcinoma cells MCF-7, and Chinese hamster cells CHO wer...The dynamic distribution of phosphorylated Histone H3 on Ser10 (phospho-H3) in cells was investigated to determineits function during mitosis. Human breast adenocarcinoma cells MCF-7, and Chinese hamster cells CHO were analyzedby indirect immunofluorescence staining with an antibody against phospho-H3. We found that the phosphorylationbegins at early prophase, and spreads throughout the chromosomes at late prophase. At metaphase, most of the phospho-H3 aggregates at the end of the condensed entity of chromosomes at equatorial plate. During anaphase and telophase,the fluorescent signal of phospho-H3 is detached from chromosomes into cytoplasm. At early anaphase, phospho-H3shows ladder bands between two sets of separated chromosome, and forms “sandwich-like structure” when the chro-mosomes condensed. With the cleavage progressing, the “ladders” of the histone contract into a bigger bright dot. Thenthe histone aggregates and some of compacted microtubules in the midbody region are composed into a “bar-like”complex to separate daughter cells. The daughter cells seal their plasma membrane along with the ends of the “bar”,inside which locates microtubules and modified histones, to finish the cytokinesis and keep the “bar complex” out of thecells. The specific distribution and kinetics of phospho-H3 in cytoplasm suggest that the modified histones may takepart in the formation of midbody and play a crucial role in cytokinesis.展开更多
LHCII is a crucial light-harvesting pigment/protein complex in photosystem II (PSII) supercomplex. It also participates in the light energy redistribution between photosystems and in the photoprotection via its revers...LHCII is a crucial light-harvesting pigment/protein complex in photosystem II (PSII) supercomplex. It also participates in the light energy redistribution between photosystems and in the photoprotection via its reversible dissociation with PSII and PSI (photosystem I). This reversible detachment of LHCII is regulated by phosphorylation of its own and PSII core protein. Under low light conditions, LHCII is phosphorylated and dissociated with PSII core protein complex and combined with PSI, which balances the excitation energy between PSII and PSI;Under high light environment, the phosphorylation of PSII core proteins makes LHCII detach from PSII. The dissociated LHCII presents in a free state, which involves in the thermal dissipation of excess excitation energy. During photodamage, dual phosphorylations of both PSII core proteins and LHCII complexes occur. The phosphorylation of D1 is conductive to the disintegration of photodamaged PSII and the cycle of repair. In this circumstance, the phosphorylation of LHCII is induced by reactive oxygen species (ROS) and then the phosphorylated LHCII migrates to PSI, into the repair cycle of damaged PSII. The ferredoxin (Fdr) and thioredoxin (Tdr) system may play a possible central role in the phosphorylation regulation on LHCII dissociation.展开更多
Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphor...Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5＇- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5＇-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by ＂second control mechanisms,＂ such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, aUosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5＇-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria similarly, decline of antioxidative enzyme activities （e.g. in the elderly） enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.展开更多
Daidzein （7,4＇-dihydroxyisoflavone） was phosphorylated by a modified Atherton-Todd reaction. The structures of the five target product, were determined by X-ray, IR, NMR and ESI-MS. Electrospray ionization results ...Daidzein （7,4＇-dihydroxyisoflavone） was phosphorylated by a modified Atherton-Todd reaction. The structures of the five target product, were determined by X-ray, IR, NMR and ESI-MS. Electrospray ionization results show that in the gas phase all the phosphorylated daidzein derivatives could form non-covalent complexes with the protein lysozyme, while non-covalent complexes were not detected in the mixed solution of daidzein with lysozyme. Relative affinity of every non-covalent complex was obtained according to its different decomposition orifice voltage.展开更多
Defects in the FAcilitates Chromatin Transcription(FACT)complex,a histone chaperone composed of SSRP1 and SUPT16H,are implicated in intellectual disability.Here,we reveal that the FACT complex promotes glycolysis and ...Defects in the FAcilitates Chromatin Transcription(FACT)complex,a histone chaperone composed of SSRP1 and SUPT16H,are implicated in intellectual disability.Here,we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain.We show that the FACT complex binds to the promoter region of the estrogen-related receptor(ERR)gene and positively regulates ERR expression.ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis.Dysfunction of the FACT complex leads to the downregulation of ERR transcription,resulting in a decreased ratio of glycolysis to oxidative phosphorylation(G/O)in neuroblasts.Consequently,neuroblasts exhibit smaller cell sizes,lower proliferation potential,and altered cell fates.Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex.Thus,the G/O ratio,mediated by the FACT complex,plays a crucial role in neuroblast cell fate maintenance.Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.展开更多
目的研究核糖体S6蛋白磷酸化(ribosomal S6 protein phosphorylation,P-S6)和细胞周期蛋白D1(CyclinD1)在翼状胬肉中的表达及相关性,探讨哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)信号通路在翼...目的研究核糖体S6蛋白磷酸化(ribosomal S6 protein phosphorylation,P-S6)和细胞周期蛋白D1(CyclinD1)在翼状胬肉中的表达及相关性,探讨哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)信号通路在翼状胬肉发病机制中的作用。方法收集翼状胬肉组织31例,正常结膜组织17例,利用免疫组织化学和Western blot进行P-S6和CyclinD1的检测及比较。结果 Western blot检测6例翼状胬肉组织中P-S6蛋白/S6蛋白表达(1.196±0.101)显著高于正常结膜组织(0.295±0.056),差异有统计学意义(P<0.05)。免疫组织化学染色结果显示:翼状胬肉中P-S6、CyclinD1的阳性表达率均为100%(25/25),正常结膜组织中P-S6阳性表达率为18.2%(2/11)、CyclinD1阳性表达率为9.1%(1/11),正常结膜组织与翼状胬肉组织中P-S6与CyclinD1表达差异均有统计学意义(均为P<.05)。翼状胬肉组织中P-S6与CyclinD1的表达呈正相关(r=0.752,P<0.05)。结论 mTORC1信号通路在翼状胬肉发病过程中起重要作用,并可能通过调控CyclinD1的表达来实现。展开更多
呼吸链的氧化磷酸化.系统由五种蛋白质—脂类的酶复合体组成:复合体Ⅰ——NADH:泛醌氧化还原酶;复合体Ⅱ——琥珀酸:泛醌氧化还原酶;复合体Ⅲ——泛醌醇:高铁细胞色素 C 氧化还原酶;复合体Ⅳ——亚铁细胞色素 C 氧化还原酶;复合体Ⅴ——...呼吸链的氧化磷酸化.系统由五种蛋白质—脂类的酶复合体组成:复合体Ⅰ——NADH:泛醌氧化还原酶;复合体Ⅱ——琥珀酸:泛醌氧化还原酶;复合体Ⅲ——泛醌醇:高铁细胞色素 C 氧化还原酶;复合体Ⅳ——亚铁细胞色素 C 氧化还原酶;复合体Ⅴ——ATP 合成酶。本文介绍了上述五个复合体的结构和功能研究进展,并用形象的图来表达它们的概念,如图1所示,从功能上来看,线粒体的氧化—磷酸化系统的五种酶复合体是相互作用着的.呼吸链的电子载体都是醌式结构(FMN、FAD、COQ)和过渡金属的复合物(铁硫蛋白等)。展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.81960732 and 82060733)the Natural Science Foundation of Jiangxi Province(No.20224BAB206111)+2 种基金the Science and Technology Plan of Jiangxi Provincial Health Commission(No.202311141)the Open Project of Jiangxi Provincial Key Laboratory of Drug Design and Evaluation(No.JKLDE-KF-2101)the Open Project of Key Laboratory of Modern Preparation of TCM,Ministry of Education,Jiangxi University of Chinese Medicine(No.TCM-201911).
文摘Objective:Cymbopogon citratus(DC.)Stapf is a medicinal and edible herb that is widely used for the treatment of gastric,nervous and hypertensive disorders.In this study,we investigated the cardioprotective effects and mechanisms of the essential oil,the main active ingredient of Cymbopogon citratus,on isoproterenol(ISO)-induced cardiomyocyte hypertrophy.Methods:The compositions of Cymbopogon citratus essential oil(CCEO)were determined by gas chromatography-mass spectrometry.Cardiomyocytes were pretreated with 16.9µg/L CCEO for 1 h followed by 10µmol/L ISO for 24 h.Cardiac hypertrophy-related indicators and NLRP3 inflammasome expression were evaluated.Subsequently,transcriptome sequencing(RNA-seq)and target verification were used to further explore the underlying mechanism.Results:Our results showed that the CCEO mainly included citronellal(45.66%),geraniol(23.32%),and citronellol(10.37%).CCEO inhibited ISO-induced increases in cell surface area and protein content,as well as the upregulation of fetal gene expression.Moreover,CCEO inhibited ISO-induced NLRP3 inflammasome expression,as evidenced by decreased lactate dehydrogenase content and downregulated mRNA levels of NLRP3,ASC,CASP1,GSDMD,and IL-1β,as well as reduced protein levels of NLRP3,ASC,pro-caspase-1,caspase-1(p20),GSDMD-FL,GSDMD-N,and pro-IL-1β.The RNA-seq results showed that CCEO inhibited the increase in the mRNA levels of 26 oxidative phosphorylation complex subunits in ISO-treated cardiomyocytes.Our further experiments confirmed that CCEO suppressed ISO-induced upregulation of mt-Nd1,Sdhd,mt-Cytb,Uqcrq,and mt-Atp6 but had no obvious effects on mt-Col expression.Conclusion:CCEO inhibits ISO-induced cardiomyocyte hypertrophy through the suppression of NLRP3 inflammasome expression and the regulation of several oxidative phosphorylation complex subunits.
文摘Diethyl flavon-7-yl phosphate was synthesized by modified Atheron-Todd reaction. The result of ESI shows that the phosphated flavonoids possess stronger binding affinities toward proteins such as myoglobin, insulin and lysozyme and are easier to form the non-covalent complexes with them.
文摘The dynamic distribution of phosphorylated Histone H3 on Ser10 (phospho-H3) in cells was investigated to determineits function during mitosis. Human breast adenocarcinoma cells MCF-7, and Chinese hamster cells CHO were analyzedby indirect immunofluorescence staining with an antibody against phospho-H3. We found that the phosphorylationbegins at early prophase, and spreads throughout the chromosomes at late prophase. At metaphase, most of the phospho-H3 aggregates at the end of the condensed entity of chromosomes at equatorial plate. During anaphase and telophase,the fluorescent signal of phospho-H3 is detached from chromosomes into cytoplasm. At early anaphase, phospho-H3shows ladder bands between two sets of separated chromosome, and forms “sandwich-like structure” when the chro-mosomes condensed. With the cleavage progressing, the “ladders” of the histone contract into a bigger bright dot. Thenthe histone aggregates and some of compacted microtubules in the midbody region are composed into a “bar-like”complex to separate daughter cells. The daughter cells seal their plasma membrane along with the ends of the “bar”,inside which locates microtubules and modified histones, to finish the cytokinesis and keep the “bar complex” out of thecells. The specific distribution and kinetics of phospho-H3 in cytoplasm suggest that the modified histones may takepart in the formation of midbody and play a crucial role in cytokinesis.
文摘LHCII is a crucial light-harvesting pigment/protein complex in photosystem II (PSII) supercomplex. It also participates in the light energy redistribution between photosystems and in the photoprotection via its reversible dissociation with PSII and PSI (photosystem I). This reversible detachment of LHCII is regulated by phosphorylation of its own and PSII core protein. Under low light conditions, LHCII is phosphorylated and dissociated with PSII core protein complex and combined with PSI, which balances the excitation energy between PSII and PSI;Under high light environment, the phosphorylation of PSII core proteins makes LHCII detach from PSII. The dissociated LHCII presents in a free state, which involves in the thermal dissipation of excess excitation energy. During photodamage, dual phosphorylations of both PSII core proteins and LHCII complexes occur. The phosphorylation of D1 is conductive to the disintegration of photodamaged PSII and the cycle of repair. In this circumstance, the phosphorylation of LHCII is induced by reactive oxygen species (ROS) and then the phosphorylated LHCII migrates to PSI, into the repair cycle of damaged PSII. The ferredoxin (Fdr) and thioredoxin (Tdr) system may play a possible central role in the phosphorylation regulation on LHCII dissociation.
基金supported by grant NoMSM0021620849 given by the Ministry of Education,Youth and Sports of the Czech Republicby project PRVOUK-P26/LF1/4given by Charles University in Prague+1 种基金by grant No. SVV-2012-264514 from Charles University in Pragueby grant No.41310 given by the Grant Agency of Charles University in Prague,Czech Republic
文摘Distribution and activity of mitochondda are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5＇- triphosphate production is regulated by many control mechanism-firstly by oxygen, substrate level, adenosine-5＇-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by ＂second control mechanisms,＂ such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, aUosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5＇-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria similarly, decline of antioxidative enzyme activities （e.g. in the elderly） enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.
基金Project supported by the National Natural Science Foundation of China （Nos. 20132020 and 20175026） and Henan Academic Foundation of Science and Technology.
文摘Daidzein （7,4＇-dihydroxyisoflavone） was phosphorylated by a modified Atherton-Todd reaction. The structures of the five target product, were determined by X-ray, IR, NMR and ESI-MS. Electrospray ionization results show that in the gas phase all the phosphorylated daidzein derivatives could form non-covalent complexes with the protein lysozyme, while non-covalent complexes were not detected in the mixed solution of daidzein with lysozyme. Relative affinity of every non-covalent complex was obtained according to its different decomposition orifice voltage.
基金supported by grants from the National Key R&D Program of China(2018YFC1004904 and 2013CB945601).
文摘Defects in the FAcilitates Chromatin Transcription(FACT)complex,a histone chaperone composed of SSRP1 and SUPT16H,are implicated in intellectual disability.Here,we reveal that the FACT complex promotes glycolysis and sustains the correct cell fate of neural stem cells/neuroblasts in the Drosophila 3rd instar larval central brain.We show that the FACT complex binds to the promoter region of the estrogen-related receptor(ERR)gene and positively regulates ERR expression.ERR is known to act as an aerobic glycolytic switch by upregulating the enzymes required for glycolysis.Dysfunction of the FACT complex leads to the downregulation of ERR transcription,resulting in a decreased ratio of glycolysis to oxidative phosphorylation(G/O)in neuroblasts.Consequently,neuroblasts exhibit smaller cell sizes,lower proliferation potential,and altered cell fates.Overexpression of ERR or suppression of mitochondrial oxidative phosphorylation in neuroblasts increases the relative G/O ratio and rescues defective phenotypes caused by dysfunction of the FACT complex.Thus,the G/O ratio,mediated by the FACT complex,plays a crucial role in neuroblast cell fate maintenance.Our study may shed light on the mechanism by which mutations in the FACT complex lead to intellectual disability in humans.
文摘目的研究核糖体S6蛋白磷酸化(ribosomal S6 protein phosphorylation,P-S6)和细胞周期蛋白D1(CyclinD1)在翼状胬肉中的表达及相关性,探讨哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)信号通路在翼状胬肉发病机制中的作用。方法收集翼状胬肉组织31例,正常结膜组织17例,利用免疫组织化学和Western blot进行P-S6和CyclinD1的检测及比较。结果 Western blot检测6例翼状胬肉组织中P-S6蛋白/S6蛋白表达(1.196±0.101)显著高于正常结膜组织(0.295±0.056),差异有统计学意义(P<0.05)。免疫组织化学染色结果显示:翼状胬肉中P-S6、CyclinD1的阳性表达率均为100%(25/25),正常结膜组织中P-S6阳性表达率为18.2%(2/11)、CyclinD1阳性表达率为9.1%(1/11),正常结膜组织与翼状胬肉组织中P-S6与CyclinD1表达差异均有统计学意义(均为P<.05)。翼状胬肉组织中P-S6与CyclinD1的表达呈正相关(r=0.752,P<0.05)。结论 mTORC1信号通路在翼状胬肉发病过程中起重要作用,并可能通过调控CyclinD1的表达来实现。
文摘呼吸链的氧化磷酸化.系统由五种蛋白质—脂类的酶复合体组成:复合体Ⅰ——NADH:泛醌氧化还原酶;复合体Ⅱ——琥珀酸:泛醌氧化还原酶;复合体Ⅲ——泛醌醇:高铁细胞色素 C 氧化还原酶;复合体Ⅳ——亚铁细胞色素 C 氧化还原酶;复合体Ⅴ——ATP 合成酶。本文介绍了上述五个复合体的结构和功能研究进展,并用形象的图来表达它们的概念,如图1所示,从功能上来看,线粒体的氧化—磷酸化系统的五种酶复合体是相互作用着的.呼吸链的电子载体都是醌式结构(FMN、FAD、COQ)和过渡金属的复合物(铁硫蛋白等)。
