Journal
AUTOPHAGY
Volume 9, Issue 4, Pages 624-625Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.23577
Keywords
autophagy; AMPK; diabetes; cardiomyopathy; apoptosis
Categories
Funding
- NCRR NIH HHS [P20 RR024215, 1P20RR024215-01] Funding Source: Medline
- NHLBI NIH HHS [R01 HL096032, HL105157, R01 HL110488, HL096032, R01 HL105157, HL110488, R01 HL080499, R01 HL089920, HL080499, R01 HL079584, R01 HL074399, HL079584, HL089920, HL074399] Funding Source: Medline
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available