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Hypoxia–reoxygenation‐induced apoptosis in cultured neonatal rat cardiomyocyets and the protective effect of prostaglandin E 1
Author(s) -
Ma Xiangqin,
Fu Runfang,
Feng Guoqing,
Wang Zhenji,
Ma Shouguo,
Weng Shiai
Publication year - 2005
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2005.04311.x
Subject(s) - hypoxia (environmental) , apoptosis , chemistry , prostaglandin , prostaglandin e , prostaglandin e2 , andrology , pharmacology , endocrinology , medicine , oxygen , biochemistry , organic chemistry
Summary 1. The aim of the present study was to investigate the effect of prostaglandin (PG) E 1 on hypoxia/re‐oxygenation (H/R) apoptosis and the expression of bcl‐2 and bax in cultured neonatal rat cardiomyocytes. 2. The H/R model was made using the first generation of cultured neonatal rat cardiomyocytes. Hypoxia/re‐oxygenation apoptosis was studied by electron microscopy and agarose gel electrophoresis. The percentage of apoptotic cells was measured by terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labeling (TUNEL). The expression of bcl‐2 and bax was detected by in situ hybridization and immunohistochemical staining. 3. Most cells of the H/R group tested by electron microscopy showed cytoplasmic concentration, nuclear chromatin condensation and margination. Prostaglandin E 1 (5, 15 and 45 μg/L) relieved the injury. The results of DNA electrophoresis in the H/R group showed a typical DNA ladder and the DNA ladder decreased gradually corresponding with increasing doses of PGE 1 . 4. The TUNEL staining showed that the total number of apoptotic cells in the H/R group was much more than that in the PGE 1 (45 μg/L) group. 5. The results of in situ hybridization and immunohistochemical staining showed that the bcl‐2 content in the H/R group was lower than that in the control group; bax content showed the reverse. Compared with the H/R group, bcl‐2 content was significantly higher in the PGE 1 (5, 15 and 45 μg/L) groups. However, bax content in the PGE 1 (5, 15 and 45 μg/L) groups was significantly lower than that in the H/R group. 6. In conclusion, H/R injury can induce cardiomyocyte apoptosis. Prostaglandin E 1 obviously has anti‐apoptotic effects on cardiomyocytes and the mechanisms probably involve the inhibition of bax expression and increased expression of bcl‐2.