Premium
Molecular adaptation to acute, chronic and intermittent hypoxia in rat hearts: a study on HIF‐1 and apoptosis
Author(s) -
Samaja Michele,
Bianciardi Paola,
Caretti Anna,
Fantacci Monica,
Ronchi Raffaella,
Milano Giuseppina
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a788-d
Subject(s) - hypoxia (environmental) , tunel assay , apoptosis , intermittent hypoxia , hypoxia inducible factors , western blot , medicine , endocrinology , biology , chemistry , gene , oxygen , biochemistry , organic chemistry , obstructive sleep apnea
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.