Molecular adaptation to acute, chronic and intermittent hypoxia in rat hearts : a study on HIF-1 and apoptosis

Hypoxia increases apoptosis through signals possibly originating from Hypoxia-Inducible Factor 1 (HIF-1). To investigate this, we exposed rats to hypoxia (10% O2 or less) in either acute (1–24 h), chronic (15 days without reoxygenating the animal for feeding, chamber cleaning etc) or intermittent (as chronic, but with 1 h/day exposure to room air) fashion and determined time course of HIF-1 (immunofluorescence and Western blot) and apoptosis (TUNEL). Results: (1) HIF-1 increases fast within 1 h hypoxia and remains constant for the following 23 h; (2) reoxygenation reduces HIF-1 to baseline levels within 1 h; (3) the next exposure to hypoxia increases HIF-1 as the first exposure; (4) after 15 days of either intermittent and chronic hypoxia, HIF-1 reduces to 10% as that measured under acute hypoxia. Of interest, the number of TUNEL-positive nuclei, or apoptosis: (1) increases slower than HIF-1, as expected; (2) remains sustained even after 15 days of either chronic or intermittent hypoxia; (3) is higher in chronic than intermittent hypoxia despite same HIF-1 level. These observations are useful to assess the molecular mechanisms underlying HIF-1, apoptosis and the oxidative damage associated with intermittent hypoxia.