Journal
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
Volume 53, Issue 3, Pages 248-257Publisher
SPRINGER
DOI: 10.1007/s11626-016-0105-2
Keywords
PGAM5; Keap1; Bcl-xL; Myocardial ischemia/reperfusion; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [81202368, 31270802, 81401365]
- Nantong science and technology project [MS12015056]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Phosphoglycerate mutase 5 (PGAM5) is a mitochondrial membrane protein that plays crucial roles in necroptosis and apoptosis. Though PGAM5 is known to be required for inducing intrinsic apoptosis through interacting with BCL2 associated X protein (Bax) and dynamin-related protein 1 (Drp1), the expression and role of PGAM5 in cardiomyocyte apoptosis driven by myocardial ischemia/reperfusion injury(MIRI) has not been studied. The present study shows that PGAM5 expression decreased after MIRI in vivo, positively correlated with Bcl-xL expression, negatively correlated with Kelch-ECH associating protein 1 (Keap1) expression. Furthermore, PGAM5 expression also decreased in cardiomyocytes after hypoxia/reoxygenation (H/R) treatment in vitro. PGAM5 silence promoted cardiomyocyte apoptosis and inhibited Bcl-xL expression, but with no effect on Keap1 expression. Accordingly, Keap1 overexpression further inhibited Bcl-xL and PGAM5 expression. Additionally, PGAM5-Bcl-xL-Keap1 interaction was identified, suggesting that PGAM5 might participate in the degradation of Bcl-xL mediated by Keap1. In summary, PGAM5 controls cardiomyocyte apoptosis induced by MIRI through regulating Keap1-mediated Bcl-xL degradation, which may supply a novel molecular target for acute myocardial infarction (AMI) therapy.
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