Open AccessEffects of short‐chain acyl‐CoA dehydrogenase on cardiomyocyte apoptosis
Author(s) -
Zeng Zhenhua,
Huang Qiuju,
Shu Zhaohui,
Liu Peiqing,
Chen Shaorui,
Pan Xuediao,
Zang Linquan,
Zhou Sigui
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12828
Subject(s) - apoptosis , ampk , activator (genetics) , peroxisome , chemistry , medicine , endocrinology , protein kinase a , microbiology and biotechnology , kinase , biology , receptor , biochemistry
Short‐chain acyl‐CoA dehydrogenase ( SCAD ), a key enzyme of fatty acid β‐oxidation, plays an important role in cardiac hypertrophy. However, its effect on the cardiomyocyte apoptosis remains unknown. We aimed to determine the role of SCAD in tert‐butyl hydroperoxide ( tBHP )‐induced cardiomyocyte apoptosis. The mRNA and protein expression of SCAD were significantly down‐regulated in the cardiomyocyte apoptosis model. Inhibition of SCAD with si RNA ‐1186 significantly decreased SCAD expression, enzyme activity and ATP content, but obviously increased the content of free fatty acids. Meanwhile, SCAD si RNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP , such as the increase in cell apoptotic rate, the activation of caspase3 and the decrease in the Bcl‐2/Bax ratio, which showed that SCAD may play an important role in primary cardiomyocyte apoptosis. The changes of phosphonate AMP‐activated protein kinase α (p‐ AMPK α) and Peroxisome proliferator‐activated receptor α ( PPAR α) in cardiomyocyte apoptosis were consistent with that of SCAD . Furthermore, PPAR α activator fenofibrate and AMPK α activator AICAR treatment significantly increased the expression of SCAD and inhibited cardiomyocyte apoptosis. In conclusion, for the first time our findings directly demonstrated that SCAD may be as a new target to prevent cardiomyocyte apoptosis through the AMPK / PPAR α/ SCAD signal pathways.