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REGULAR ARTICLES
Cell Research (2003); 13(5):385-391 |
Intermittent hypoxia
attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating
Bcl-2/Bax expression
JIAN WEN DONG1,
HAI FENG ZHU1, WEI ZHONG ZHU1, HAI LEI DING1,
TIE MIN MA2, ZHAO NIAN ZHOU1*
1Laboratory
of Hypoxic Cardiovascular Physiology, Shanghai Institutes for Biological Sciences,Chinese
Academy of Sciences, Shanghai 200031, China. E-mail: znzhou@server.shcnc.ac.cn
2Department of Physiology
and Pathophysiology, Health Science Center Peking University, Beijing 100083,
China.
*Correspondence:
Prof. Zhao Nian ZHOU, Laboratory of Hypoxic Cardiovascular Physiology, Shanghai
Institutes for Biological Sciences,Chinese Academy of Sciences, 320 Yueyang
Road, Shanghai 200031,China. Tel:
86-21-5492-0305, Fax: 86-21-5492-0306, E-mail:
znzhou@server.shcnc.ac.cn
Received March-4-2003
Revised Aug-11-2003 Accepted Sep-15-2003
ABSTRACT
Intermittent hypoxia has been
shown to provide myocardial protection against ishemia/reperfusion-induced injury.
Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion
injury. Our aim was to investigate whether intermittent hypoxia could attenuate
ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential
mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated
5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats
were kept under normoxic conditions. Isolated perfused hearts from both groups
were subjected to 30 min of global ischemia followed by 60 min reperfusion.
Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl
transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis.
Expressions of apoptosis related proteins, Bax and Bcl-2, in cytosolic and membrane
fraction were detected by Western Blotting. After ischemia/reperfusion, enhanced
recovery of cardiac function was observed in intermittent hypoxia hearts compared
with normoxia group. Ischemia/reperfusion-induced apoptosis, as evidenced by
TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent
hypoxia group compared with normoxia group. After ischemia/reperfusion, expression
of Bax in both cytosolic and membrane fractions was decreased in intermittent
hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did
not induce changes in the level of Bcl-2 expression in cytosolic fraction between
intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane
fraction was upregulated in intermittent hypoxia group compared with normoxia
group. These results indicated that the cardioprotection of intermittent hypoxia
against ischemia/reperfusion injury appears to be in part due to reduce myocardial
apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis
via increasing the ratio of Bcl-2/Bax, especially in membrane fraction.
Keywords: intermittent
hypoxia, apoptosis, cardiac myocytes, Bax, Bcl-2.
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