典型文献
S-nitrosylation of Hsp90 promotes cardiac hypertrophy in mice through GSK3β signaling
文献摘要：
Cardiac hypertrophy,as one of the major predisposing factors for chronic heart failure,lacks effective interventions.Exploring the pathogenesis of cardiac hypertrophy will reveal potential therapeutic targets.S-nitrosylation is a kind of posttranslational modification that occurs at active cysteines of proteins to mediate various cellular processes.We here identified heat shock protein 90(Hsp90)as a highly S-nitrosylated target in the hearts of rodents with hypertrophy,and the role of Hsp90 in cardiac hypertrophy remains undefined.The S-nitrosylation of Hsp90(SNO-Hsp90)levels were elevated in angiotensin Ⅱ(Ang Ⅱ)-or phenylephrine(PE)-treated neonatal rat cardiomyocytes(NRCMs)in vitro as well as in cardiomyocytes isolated from mice subjected to transverse aortic constriction(TAC)in vivo.We demonstrated that the elevated SNO-Hsp90 levels were mediated by decreased S-nitrosoglutathione reductase(GSNOR)expression during cardiac hypertrophy,and delivery of GSNOR adeno-associated virus expression vectors(AAV9-GSNOR)decreased the SNO-Hsp90 levels to attenuate cardiac hypertrophy.Mass spectrometry analysis revealed that cysteine 589(Cys589)might be the S-nitrosylation site of Hsp90.Delivery of the mutated AAV9-Hsp90-C589A inhibited SNO-Hsp90 levels and attenuated cardiac hypertrophy.We further revealed that SNO-Hsp90 led to increased interaction of glycogen synthase kinase 3β(GSK3β)and Hsp90,leading to elevated GSK3β phosphorylation and decreased eIF2Bs phosphorylation,thereby aggravating cardiac hypertrophy.Application of GSK3β inhibitor TWS119 abolished the protective effect of Hsp90-C589A mutation in Ang Ⅱ-treated NRCMs.In conclusion,this study demonstrates a critical role of SNO-Hsp90 in cardiac hypertrophy,which may be of a therapeutic target for cardiac hypertrophy treatment.
文献关键词：
中图分类号：
作者姓名：
Shuang Zhao;Tian-yu Song;Zi-yu Wang;Jie Gao;Jia-wei Cao;Lu-lu Hu;Zheng-rong Huang;Li-ping Xie;Yong Ji
作者机构：
Key Laboratory of Cardiovascular and Cerebrovascular Medicine,Nanjing Medical University,Nanjing 210029,China;Key Laboratory of Targeted Intervention of Cardiovascular Disease,Collaborative Innovation Center for Cardiovascular Disease Translational Medicine,Nanjing Medical University,Nanjing 210029,China;Department of Cardiology,The First Affiliated Hospital of Xiamen University,Xiamen 361003,China
文献出处：
引用格式：
[1]Shuang Zhao;Tian-yu Song;Zi-yu Wang;Jie Gao;Jia-wei Cao;Lu-lu Hu;Zheng-rong Huang;Li-ping Xie;Yong Ji-.S-nitrosylation of Hsp90 promotes cardiac hypertrophy in mice through GSK3β signaling)[J].中国药理学报（英文版）,2022(08):1979-1988
A类：
nitrosylation,nitrosylated,nitrosoglutathione,Cys589,C589A,eIF2Bs,TWS119
B类：
Hsp90,promotes,cardiac,hypertrophy,mice,through,GSK3,signaling,Cardiac,major,predisposing,factors,chronic,failure,lacks,effective,interventions,Exploring,pathogenesis,will,potential,therapeutic,targets,kind,posttranslational,modification,that,occurs,active,cysteines,proteins,various,cellular,processes,We,identified,heat,shock,highly,hearts,rodents,role,remains,undefined,levels,were,elevated,angiotensin,Ang,phenylephrine,PE,treated,neonatal,cardiomyocytes,NRCMs,vitro,well,isolated,from,subjected,transverse,aortic,constriction,TAC,vivo,demonstrated,mediated,decreased,reductase,GSNOR,expression,during,delivery,adeno,associated,virus,vectors,AAV9,Mass,spectrometry,analysis,revealed,might,be,site,Delivery,mutated,inhibited,attenuated,further,increased,interaction,glycogen,synthase,kinase,leading,phosphorylation,thereby,aggravating,Application,inhibitor,abolished,protective,mutation,In,conclusion,this,study,demonstrates,critical,which,may,treatment
AB值：
0.452118
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