title: 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-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.
authors.affiliation: School of Physical Therapy, Chung-Shan Medical University, Taichung, Taiwan.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: James A
authors.initials: JA
authors.lastname: Lin
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Chu
authors.forename: Chin-Kun
authors.initials: CK
authors.lastname: Wang
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.forename: Shyi-Gang P
authors.initials: SG
authors.lastname: Wang
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.forename: Mu-Hsin
authors.initials: MH
authors.lastname: Chang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: 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*
chemical_list: D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053148:Caspase 3