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題名 | Effects of Norepinephrine on Apoptosis in Rat Neonatal Cardiomyocytes=Norepinephrine 對新生兒心肌細胞的凋零死亡作用 |
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作者 | 徐國基; 管培良; 張美玲; 王葆瑋; 黃芳彥; Shyu, Kou-gi; Kuan, Peiliang; Chang, Mei-ling; Wang, Bao-wei; Huang, Fan-yen; |
期刊 | 臺灣醫學會雜誌 |
出版日期 | 20000500 |
卷期 | 99:5 2000.05[民89.05] |
頁次 | 頁412-418 |
分類號 | 417.517 |
語文 | eng |
關鍵詞 | 新生兒; 心肌細胞; 細胞凋零; Apoptosis; Myocytes; Norepinephrine; Adrenergic antagonist; Mcl-1; |
英文摘要 | Background and purpose: Norepinephrine (NE) is elevated in heart failure and can induce apoptosis in adult cardiac myocytes. However, it is not known whether NE can induce apoptosis in neonatal cardiac myocytes. This study examined the ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes in vitro. Methods: Neonatal rat cardiac myocytes were exposed to NE alone, NE + propranolol, or NE + prazosin for 24 hours. Apoptosis was assayed by DNA laddering with agarose gel electrophoresis and immunofluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Reverse transcription polymerase chain reaction was used to evaluate the expression of Mcl-1. Creatine kinase activity in the cultured medium was used as a measure of the toxicity of NE on myocytes. Results: NE increased DNA laddering on agarose gel electrophoresis and increased the number of apoptotic cells in a dose-dependent manner. No increase in apoptosis was found in response to NE doses between 1 and 50 �禦ol/L. NE at concentrations of 100 to 400 �禦ol/L increased apoptosis from 10% to 31% of cells. The ability of NE to stimulate apoptosis in rat neonatal cardiac myocytes was completely blocked by propranolol, but not prazosin. NE treatment at high concentrations sharply reduced the level of Mcl-1 mRNA, coincident with the increase in the number of apoptotic cells. Creatine kinase activity in the cultured medium was similar among the controls and NE-treated myocytes. Conclusions: Our results showed that NE at high concentrations stimulated apoptosis in rat neonatal cardiac myocytes in vitro. Apoptosis induced by NE was associated with down-regulation of Mcl-1. However, NE at the same concentration was not toxic to rat neonatal cardiac myocytes. |
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