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
中科院分区:
文献类型:
--
作者:
Burniston JG;Chester N;Clark WA;Tan LB;Goldspink DF
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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