Abstract:

BACKGROUND: Hypoxic exercise can upregulate uncoupling proteins 3 expression, and promote the resistance of skeletal muscle mitochondria to hypoxia, but its biological effect and mechanism are still unclear.  
OBJECTIVE: To observe the effect of hypoxia alone and hypoxic exercise on mitochondrial energetics and uncoupling proteins 3 expression, and to discuss the biological effect of NO-ATF1 signaling pathway in this process.
METHODS: Sixty SD rats were randomly divided into five groups: normoxia control group, hypoxia group, hypoxic exercise group, hypoxia + L-NAME group and hypoxic exercise + L-NAME group. Animals in the hypoxia group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3% O₂. Those in the hypoxic exercise groups were exercised on a motor-driven rodent treadmill in the normobaric hypoxic tent with11.3% O₂. And the drinking water for L-NAME animals contained L-NAME at dose of 1 g/L. All these interventions lasted for 4 weeks. The content of nitric oxide (NO) was measured with nitrate reductase method. Adenodine triphospate (ATP) synthesis capacity was determined using a bioluminescence technique. Mitochondrial H2O2 generation was determined using dichlorofluorescein (DCF). The expression of uncoupling proteins 3 (UCP3) and ATF1 in muscle were detected by real-time quantitative PCR. And the phosphorylation of ATF1 and mitochondrial UCP3 protein expression were measured by Western-blotting. 
RESULTS AND CONCLUSION: Exercise training in hypoxia markedly enhanced mitochondrial UCP3 expression and ATP synthesis capacity, and suppressed mitochondrial H₂O₂ generation, which accompanied with elevated NO content and ATF1 phosphorylation level. L-NAME restrained the protective effect of hypoxic exercise on mitochondria. These findings indicated that hypoxic exercise can increase uncoupling proteins 3 expression through the NO-ATF1 signaling pathway so as to increase the mitochondrial resistance to hypoxia.