典型文献
Connexin 43 hyper-phosphorylation at serine 282 triggers apoptosis in rat cardiomyocytes via activation of mitochondrial apoptotic pathway
文献摘要：
Cx43 is the major connexin in ventricular gap junctions,and plays a pivotal role in control of electrical and metabolic communication among adjacent cardiomyocytes.We previously found that Cx43 dephosphorylation at serine 282(pS282)caused cardiomyocyte apoptosis,which is involved in cardiac ischemia/reperfusion injury.In this study we investigated whether Cx43-S282 hyper-phosphorylation could protect cardiomyocytes against apoptosis.Adenovirus carrying rat full length Cx43 gene(Cx43-wt)or a mutant gene at 5282 substituted with aspartic acid(S282D)were transfected into neonatal rat ventricular myocytes(NRVMs)or injected into rat ventricular wall.Rat abdominal aorta constriction model(AAC)was used to assess Cx43-S282 phosphorylation status.We showed that Cx43 phosphorylation at S282 was increased over 2-times compared to Cx43-wt cells at 24 h after transfection,while pS262 and pS368 were unaltered.S282D-transfected cells displayed enhanced gap junctional communication,and increased basal intracellular Ca2+concentration and spontaneous Ca2+transients compared to Cx43-wt cells.However,spontaneous apoptosis appeared in NRVMs transfected with S282D for 34 h.Rat ventricular myocardium transfected with S282D in vivo also exhibited apoptotic responses,including increased Bax/Bcl-xL ratio,cytochrome c release as well as caspase-3 and caspase-9 activities,while factor-associated suicide(Fas)/Fas-associated death domain expression and caspase-8 activity remained unaltered.In addition,AAC-induced hypertrophic ventricles had apoptotic injury with Cx43-S282 hyper-phosphorylation compared with Sham ventricles.In conclusion,Cx43 hyper-phosphorylation at S282,as dephosphorylation,also triggers cardiomyocyte apoptosis,but through activation of mitochondrial apoptosis pathway,providing a fine-tuned Cx43-S282 phosphorylation range required for the maintenance of cardiomyocyte function and survival.
文献关键词：
中图分类号：
作者姓名：
Zhi-ping Fu;Lu-lin Wu;Jing-yi Xue;Lan-e Zhang;Chen Li;Hong-jie You;Da-li Luo
作者机构：
Department of Pharmacology,School of Basic Medical Sciences,Beijing Key Laboratory of Metabolic Disturbance Related Cardiovascular Disease,Capital Medical University,Beijing 100069,China
文献出处：
引用格式：
[1]Zhi-ping Fu;Lu-lin Wu;Jing-yi Xue;Lan-e Zhang;Chen Li;Hong-jie You;Da-li Luo-.Connexin 43 hyper-phosphorylation at serine 282 triggers apoptosis in rat cardiomyocytes via activation of mitochondrial apoptotic pathway)[J].中国药理学报（英文版）,2022(08):1970-1978
A类：
pS282,S282,S282D,NRVMs,pS262,pS368,Ca2+transients
B类：
Connexin,serine,triggers,apoptosis,cardiomyocytes,via,activation,mitochondrial,apoptotic,pathway,Cx43,major,connexin,ventricular,gap,junctions,plays,pivotal,role,control,electrical,metabolic,communication,among,adjacent,We,previously,found,that,dephosphorylation,caused,which,involved,cardiac,ischemia,reperfusion,injury,In,this,study,investigated,whether,could,protect,against,Adenovirus,carrying,full,length,gene,wt,mutant,substituted,aspartic,acid,were,transfected,into,neonatal,injected,wall,Rat,abdominal,aorta,constriction,model,AAC,was,assess,status,showed,increased,over,times,compared,cells,after,transfection,while,unaltered,displayed,enhanced,junctional,basal,intracellular,Ca2+concentration,spontaneous,However,appeared,myocardium,vivo,also,exhibited,responses,including,Bax,Bcl,xL,cytochrome,release,well,caspase,activities,associated,suicide,Fas,death,domain,expression,activity,remained,addition,induced,hypertrophic,ventricles,had,Sham,conclusion,but,through,providing,fine,tuned,range,required,maintenance,function,survival
AB值：
0.465825
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