title: Regulation of interplay between autophagy and apoptosis in the diabetic heart: new role of AMPK.
abstract: Diabetes induces cardiomyocyte apoptosis and suppresses cardiac autophagy, indicating that the interplay between autophagy and apoptotic cell death pathways is important in the pathogenesis of diabetic cardiomyopathy. The potential mechanism, however, remains unknown. We recently reported that diabetes depresses AMP-activated protein kinase (AMPK) activity, inhibits MAPK8/JNK1-BCL2 signaling, and promotes the interaction between BECN1 and BCL2. Concomitantly, diabetes induces cardiomyocyte apoptosis and suppresses cardiac autophagy. Activation of AMPK directly phosphorylates MAPK8, which mediates BCL2 phosphorylation and subsequent BECN1-BCL2 dissociation, leading to restoration of cardiac autophagy, protection against cardiac apoptosis, and ultimately improvement in cardiac structure and function. We conclude that dissociation of BCL2 from BECN1 through activation of MAPK8-BCL2 signaling may be an important mechanism by which AMPK activation restores autophagy, protects against cardiac apoptosis, and prevents diabetic cardiomyopathy.
authors: Section of Molecular Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors: Ming-Hui
authors: MH
authors: Zou
authors: Zhonglin
authors: Z
authors: Xie
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D058065:Diabetic Cardiomyopathies / Q000201:enzymology* / Q000473:pathology*; D006706:Homeostasis; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D015398:Signal Transduction
chemical_list: D055372:AMP-Activated Protein Kinases
keywords: AMPK; apoptosis; autophagy; cardiomyopathy; diabetes