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Phenylephrine protects cardiomyocytes from starvation‐induced apoptosis by increasing glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) activity
Author(s) -
Yao LingLing,
Wang YongGang,
Liu XiuJie,
Zhou Yu,
Li Na,
Liu Jun,
Zhu YiChun
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24053
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , tunel assay , apoptosis , microbiology and biotechnology , cytochrome c , mitochondrion , myocyte , biology , chemistry , dehydrogenase , biochemistry , enzyme
Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is known to be a “housekeeping” protein; studies in non‐cardiomyocytic cells have shown that GAPDH plays pro‐apoptotic role by translocating from cytoplasm to the nucleus or to the mitochondria. However, the cardiovascular roles of GAPDH are unknown. We observed that phenylephrine (PE) (100 µM) protected against serum and glucose starvation ‐induced apoptosis in neonatal rat cardiac myocytes as assessed by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) and mitochondrial membrane potential depolarization. GAPDH glycolysis activity was positively correlated with the antiapoptotic action of PE. GAPDH activity inhibition blunted PE‐induced protection of the mitochondrial membrane potential and cardiomyocytes. PE‐induced Bcl‐2 protein increase, Bax mitochondrial decrease and inhibition of cytochrome C release and Caspase 3 activation, as well as ROS production were blunted by GAPDH activity inhibition. Moreover, GAPDH overexpression provided protection against starvation‐induced cardiomyocyte apoptosis in vitro and ischemia‐induced cardiac infarction in vivo. Inhibition of Akt prevented PE‐induced GAPDH activity increase and cardiomyocytes protection. In conclusion, the present study provides the first direct evidence of an antiapoptotic role of GAPDH in PE‐induced cardiomyocytes protection; GAPDH activity elevation mainly affects the mitochondria‐induced apoptosis. J. Cell. Physiol. 227: 3518–3527, 2012. © 2012 Wiley Periodicals, Inc.