Effects of long-term intermittent hypoxia on mitochondrial and Fas death receptor dependent apoptotic pathways in rat hearts.
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% O(2), 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.
Lee
Shin-Da
SD
School of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan.
Kuo
Wei-Wen
WW
Lin
James A
JA
Chu
Yu-Fang
YF
Wang
Chin-Kun
CK
Yeh
Yu-Lan
YL
Wang
Shyi-Gang P
SG
Liu
Jer-Yuh
JY
Chang
Mu-Hsin
MH
Huang
Chih-Yang
CY
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D009202:Cardiomyopathies / Q000209:etiology; D053148:Caspase 3; D053200:Fas-Associated Death Domain Protein; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053148:Caspase 3