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% 02, 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 proapoptotic 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.