Dose-dependent apoptotic and necrotic myocyte death induced by the beta2-adrenergic receptor agonist, clenbuterol.

Dose-dependent apoptotic and necrotic myocyte death induced by the beta2-adrenergic receptor agonist, clenbuterol.
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DOI:
10.1002/mus.20407
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发表时间:
2005-12
期刊:
影响因子:
3.4
通讯作者:
Goldspink DF
Goldspink DF
中科院分区:
医学3区
文献类型:
--
作者:
Burniston JG;Chester N;Clark WA;Tan LB;Goldspink DF

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我们研究了β2-肾上腺素能受体激动剂克仑特罗诱导的心肌细胞凋亡和坏死的剂量和时间依赖性,目的是确定心肌细胞凋亡和坏死是两个独立的过程还是一个连续的事件。雄性Wistar大鼠皮下注射克伦特罗,免疫组化检测肌细胞特异性凋亡和坏死。给予克仑特罗后 4 小时,心肌细胞凋亡达到峰值,12 小时后细胞坏死。在比目鱼肌中,10 μg 克伦特罗 kg-1 诱导峰值凋亡(5.8 ± 2.0 %;P<0.05),5 mg 克伦特罗 kg-1 诱导峰值坏死(7.4 ± 1.7 %;P<0.05)。服用克仑特罗 12 小时后,73% 的受损心肌细胞标记为坏死,27% 标记为凋亡和坏死,没有标记为纯粹凋亡。每天两次给予 10 μg 克仑特罗 kg-1,在 8 天内诱导累积的心肌细胞死亡。这些数据表明,心肌细胞死亡的表型取决于损伤的程度和研究的时间。只有非常低的剂量仅诱导细胞凋亡,大多数情况下凋亡的肌细胞溶解并坏死,且坏死的程度大于细胞凋亡的程度。因此,研究细胞凋亡和坏死性心肌细胞死亡非常重要,这与当前仅研究细胞凋亡的趋势相反。
We have investigated the dose- and time-dependency of myocyte apoptosis and necrosis induced by the β2-adrenergic receptor agonist, clenbuterol, with the aim of determining whether myocyte apoptosis and necrosis are two separate processes or a continuum of events. Male Wistar rats were administered subcutaneous injections of clenbuterol, and immunohistochemistry was used to detect myocyte specific apoptosis and necrosis. Myocyte apoptosis peaked 4 h after, and necrosis 12 h after, clenbuterol administration. In the soleus, peak apoptosis (5.8 ± 2.0 %; P<0.05) was induced by 10 μg and peak necrosis (7.4 ± 1.7 %; P<0.05) by 5 mg of clenbuterol kg-1. Twelve hours after clenbuterol administration, 73 % of damaged myocytes labelled as necrotic, 27 % as apoptotic and necrotic and none labelled as purely apoptotic. Bi-daily administrations of 10 μg of clenbuterol kg-1 induced cumulative myocyte death over 8 days. These data show that the phenotype of myocyte death is dependent on the magnitude of the insult and the time at which it is investigated. Only very low doses induced only apoptosis, in most cases apoptotic myocytes lysed and became necrotic and the magnitude of necrosis was greater than that of apoptosis. Thus, it is important to investigate both apoptotic and necrotic myocyte death, this being contrary to the current trend of only investigating apoptotic cell death.
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