Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts

Abstract Background It is unclear whether the cardiac mitochondrial dependent apoptotic pathways and Fas death receptor dependent apoptotic pathways will be induced by long-term intermittent hypoxia. Methods Twenty-seven Sprague-Dawley rats were randomly assigned into three groups: normoxia, long-te...

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Bibliographic Details
Published in:International journal of cardiology 2007-04, Vol.116 (3), p.348-356
Main Authors: Lee, Shin-Da, Kuo, Wei-Wen, Lin, James A, Chu, Yu-Fang, Wang, Chin-Kun, Yeh, Yu-Lan, Wang, Shyi-Gang P, Liu, Jer-Yuh, Chang, Mu-Hsin, Huang, Chih-Yang
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Biological and medical sciences
Cardiac
Cardiology. Vascular system
Cardiomyopathies - etiology
Cardiovascular
Caspase 3
Fas death receptor
fas Receptor - physiology
Fas-Associated Death Domain Protein
Hypoxia
Hypoxia - complications
Hypoxia - physiopathology
Male
Medical sciences
Mitochondria, Heart - physiology
Mitochondrial dependent pathway
Rats
Rats, Sprague-Dawley
Signal Transduction
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Summary:Abstract Background It is unclear whether the cardiac mitochondrial dependent apoptotic pathways and Fas death receptor dependent apoptotic pathways will be induced by long-term intermittent hypoxia. Methods Twenty-seven Sprague-Dawley rats were randomly assigned into three groups: normoxia, long-term intermittent hypoxia (12% O2 , 8 h/day) for 4 weeks (4WLTIH) and for 8 weeks (8WLTIH). Histological analysis, Western blotting and RT-PCR in the three groups were performed on tissue from the excised left ventricle. Results Mitochondrial dependent pro-apoptotic pathway, BNIP3, caspase 9, and caspase 3, and the Fas death receptor dependent pro-apoptotic pathway, Fas, caspase 8, and caspase 3 were all significantly increased after 4WLTIH and even further enhanced after 8WLTIH. In addition, mitochondrial related anti-apoptotic proteins, Bcl2, its upstream phosphorylated protein kinase B (Akt), and the mitochondrial key oxidative enzyme, cytochrome c oxidase, were all decreased after 4WLTIH and further reduced after 8WLTIH. Conclusions The mitochondrial dependent apoptotic pathways and Fas death receptor dependent apoptotic pathways in rat hearts were both activated by long-term intermittent hypoxia.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2006.03.064