Open AccessJournal Article
Differential Roles of GSK-3β During Myocardial Ischemia and Ischemia/Reperfusion
Reads0
Chats0
TLDR
This work studied the molecular mechanism mediating the effect of GSK-3β activation/inhibition upon myocardial injury during prolonged ischemia and I/R, and inhibited mTOR signaling and inhibited autophagy through a rapamycin-sensitiv...Abstract:
Rationale:Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated. Objective:We studied the molecular mechanism mediating the effect of GSK-3β activation/inhibition upon myocardial injury during prolonged ischemia and I/R. Methods and Results:Beta isoform–specific inhibition of GSK-3 by dominant negative GSK-3β in transgenic mice (Tg-DnGSK-3β) or in heterozygous GSK-3β knock-out mice (GSK-3β+/−) significantly increased, whereas activation of GSK-3β in constitutively active GSK-3β knock-in mice (βKI) significantly decreased, myocardial ischemic injury after prolonged ischemia. In contrast, inhibition of GSK-3β in Tg-DnGSK-3β or GSK-3β+/− significantly reduced, while activation of GSK-3β in βKI significantly enhanced, myocardial I/R injury. Inhibition of GSK-3β stimulated mTOR signaling and inhibited autophagy through a rapamycin-sensitiv...read more
Citations
More filters
Journal ArticleDOI
Mammalian Target of Rapamycin Signaling in Cardiac Physiology and Disease
TL;DR: Information is reviewed regarding the effects exerted by mTOR signaling in cardiovascular physiology and pathological states to extend life span in mammals and reduce pathological hypertrophy and heart failure caused by increased load or genetic cardiomyopathies.
Journal ArticleDOI
Mechanisms of Cell Death in Heart Disease
TL;DR: The possibility is raised that small molecules aimed at inhibiting cell death may provide novel therapies for these common and lethal heart syndromes.
Journal ArticleDOI
The A3 Adenosine Receptor: History and Perspectives
Pier Andrea Borea,Katia Varani,Fabrizio Vincenzi,Pier Giovanni Baraldi,Mojgan Aghazadeh Tabrizi,Stefania Merighi,Stefania Gessi +6 more
TL;DR: It will become apparent in the present review that purine scientists do seem to be getting closer to their goal: the incorporation of adenosine ligands into drugs with the ability to save lives and improve human health.
Journal ArticleDOI
The Cardioprotection of the Insulin-Mediated PI3K/Akt/mTOR Signaling Pathway
TL;DR: Activation of the PI3K/Akt signaling pathway induced by insulin not only inhibits cardiomyocyte apoptosis but also substantially preserves and even improves regional and overall cardiac function.
Journal ArticleDOI
Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β signaling and inhibition of the mitochondria-dependent apoptotic pathway
Yang Wang,Xu Li,Xiaoliang Wang,Wayne Bond Lau,Yajing Wang,Yuan Xing,Xing Zhang,Xin-Liang Ma,Feng Gao +8 more
TL;DR: GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway is demonstrated.
References
More filters
Journal ArticleDOI
Mammalian Target of Rapamycin Signaling in Cardiac Physiology and Disease
TL;DR: Information is reviewed regarding the effects exerted by mTOR signaling in cardiovascular physiology and pathological states to extend life span in mammals and reduce pathological hypertrophy and heart failure caused by increased load or genetic cardiomyopathies.
Journal ArticleDOI
Mechanisms of Cell Death in Heart Disease
TL;DR: The possibility is raised that small molecules aimed at inhibiting cell death may provide novel therapies for these common and lethal heart syndromes.
Journal ArticleDOI
The A3 Adenosine Receptor: History and Perspectives
Pier Andrea Borea,Katia Varani,Fabrizio Vincenzi,Pier Giovanni Baraldi,Mojgan Aghazadeh Tabrizi,Stefania Merighi,Stefania Gessi +6 more
TL;DR: It will become apparent in the present review that purine scientists do seem to be getting closer to their goal: the incorporation of adenosine ligands into drugs with the ability to save lives and improve human health.
Journal ArticleDOI
Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK-3β signaling and inhibition of the mitochondria-dependent apoptotic pathway
Yang Wang,Xu Li,Xiaoliang Wang,Wayne Bond Lau,Yajing Wang,Yuan Xing,Xing Zhang,Xin-Liang Ma,Feng Gao +8 more
TL;DR: GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway is demonstrated.
Journal ArticleDOI
bFGF regulates autophagy and ubiquitinated protein accumulation induced by myocardial ischemia/reperfusion via the activation of the PI3K/Akt/mTOR pathway
Zhouguang Wang,Yue Wang,Yan Huang,Qin Lu,Lei Zheng,Dong Hu,Wenke Feng,Yanlong Liu,Kang-Ting Ji,Hongyu Zhang,Xiaobing Fu,Xiaokun Li,Maoping Chu,Jian Xiao +13 more
TL;DR: The results indicate that the role of bFGF in myocardial I/R recovery is related to the inhibition of excessive autophagy and increased ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling.