Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte.
Oxidative stress is one of the main causes of myocardial injury, which is associated with cardiomyocyte death. Mitochondria play a key role in triggering the necrosis and apoptosis pathway of cardiomyocytes under oxidative stress. Although prohibitin (PHB) has been acknowledged as a mitochondrial chaperone, its functions in cardiomyocytes are poorly characterized. The present research was designed to investigate the cardioprotective role of PHB in mitochondria. Oxidative stress can increase the PHB content in mitochondria in a time-dependent manner. Overexpression of PHB in cultured cardiomyocytes by transfection of recombinant adenovirus vector containing PHB sense cDNA resulted in an increase of PHB in mitochondria. Compared with the non-transfection cardiomyocytes, PHB overexpression could protect the mitochondria from oxidative stress-induced injury. The mitochondria-mediated apoptosis pathway was consistently suppressed in PHB-overexpressed cardiomyocytes after hydrogen peroxide (H(2)O(2)) treatment, including a reduced change in mitochondrial membrane permeability transition and an inhibited release of cytochrome c from mitochondria to cytoplasma. As a result, the oxidative stress-induced cardiomyocyte apoptosis was suppressed. These data indicated that PHB protected the cardiomyocytes from oxidative stress-induced damage, and that increasing PHB content in mitochondria constituted a new therapeutic target for myocardium injury.
Liu
Xiaohua
X
Department of Stress Medicine, Institute of Health & Environmental Medicine, Tianjin, 300050, People's Republic of China.
Ren
Zhe
Z
Zhan
Rui
R
Wang
Xinxing
X
Wang
Xiaoming
X
Zhang
Zhiqing
Z
Leng
Xue
X
Yang
Zhihua
Z
Qian
Lingjia
L
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D008929:Mitochondria, Heart / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D000091402:Prohibitins; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D024101:Mitochondrial Proteins; C000717332:Phb protein, rat; D000091402:Prohibitins; D012097:Repressor Proteins