| Autor: |
Ito, Hiroshi, Adachi, Susumu, Tamamori, Mimi, Fujisaki, Hiroyuki, Tanaka, Masato, Lin, Meihong, Akimoto, Hajime, Marumo, Fumiaki, Hiroe, Michiaki |
| Zdroj: |
Journal of Molecular and Cellular Cardiology; June, 1996, Vol. 28 Issue: 6 p1271-1277, 7p |
| Abstrakt: |
Hypoxic or ischemic stresses on cardiomyocytes may cause a variety of compensatory responses including cell hypertrophy. In this study, we examined whether hypoxia induces hypertrophy of cardiomyocytesin vitroand whether hypoxia-induced hypertrophy is inhibited by an endothelin A receptor antagonist (BQ123). Neonatal rat cardiomyocytes were cultured in 10% O2/85% N2/5% CO2or 95% N2/5% CO2to produce a mild or severe hypoxic condition, respectively. Cardiomyocytes exposed to severe hypoxia revealed degenerative morphological changes and a decrease of cell number, suggesting the toxicity of severe hypoxia on cardiomyocytes. In contrast, cardiomyocytes with mild hypoxia developed hypertrophy; cell surface area of cardiomyocytes as evaluated by an image analyser system increased by 1.6-fold over control after 48 h. [3H]leucine incorporation into the cells was significantly increased by mild hypoxia but decreased by severe hypoxia. mRNA level of skeletalα-actin, a genetic marker of cardiac hypertrophy, up-regulated after 6–24 h by mild hypoxia. A transient increase of preproET-1 mRNA and a time-dependent increase of ET-1 protein in the culture medium were also observed in cardiomyocytes exposed to mild hypoxia. BQ123 partially inhibited either hypoxia-induced [3H]leucine incorporation or skeletalα-actin mRNA in a dose-dependent manner. These data suggest that mild hypoxia induces hypertrophy of cardiomyocytes and that activation of endogenous ET-1 may, at least in part, mediate this hypertrophic responses as an autocrine/paracrine factor. |
| Databáze: |
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