Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo:: the same or separate death pathways?
Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo:: the same or separate death pathways?
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DOI：
10.1113/expphysiol.2004.027482
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发表时间：
2004-07-01
影响因子：
2.7
通讯作者：
Tan, LB
中科院分区：
文献类型：
--
作者：
Goldspink, DF;Burniston, JG;Tan, LB
高水平的儿茶酚胺具有肌毒性，但在体内心脏和骨骼肌中尚未确定细胞凋亡和坏死的相对量。免疫组织化学被用来检测和定量心肌细胞特异性坏死（体内肌球蛋白抗体）和细胞凋亡（体外半胱天冬酶-3抗体）在心脏和比目鱼肌的雄性Wistar大鼠，接受了单次皮下注射异丙肾上腺素超过1 μ g至5 mg [kg体重（BW）]（-1）。体内单次注射5 mg（kg BW）（-1）异丙肾上腺素后3-6 h出现心肌细胞凋亡高峰，18 h出现坏死。在心脏中，肌细胞死亡通过β（1）-肾上腺素能受体介导，而比目鱼肌中的肌细胞死亡通过β（2）-肾上腺素能受体介导。心肌细胞死亡不均匀地分布在整个心脏，在左心室（LV）内膜下最大。并且在接近顶点处达到峰值，但是坏死明显多于凋亡。广泛的共定位的caspase-3和肌球蛋白标记被发现在心肌细胞的心脏和慢收缩比目鱼肌。这与类似的空间分布和对儿茶酚胺剂量的反应一起表明，在坏死和凋亡的肌细胞中发生半胱天冬酶-3活化，或者大部分凋亡的肌细胞在体内进展为继发性坏死。
High levels of catecholamines are myotoxic but the relative amounts of apoptosis and necrosis have not been established in vivo in cardiac and skeletal muscles. Immunohistochemistry was used to detect and quantify myocyte-specific necrosis (myosin antibody in vivo) and apoptosis (caspase-3 antibody in vitro) in the heart and soleus muscles of male Wistar rats that had received single subcutaneous injections of isoprenaline over the range 1 mug to 5 mg [kg body weight (BW)](-1). Peak myocyte apoptosis occurred 3-6 h after, and necrosis 18 h after, a single injection of 5 mg (kg BW)(-1) isoprenaline in vivo. In the heart myocyte death was mediated through the beta(1)-adrenergic receptor whereas myocyte death in the soleus muscle was mediated through the beta(2)-adrenergic receptor. Cardiomyocyte death was heterogeneously distributed throughout the heart, being greatest in the left ventricle (LV) subendocardium. and peaking close to the apex, but with significantly more necrosis than apoptosis. Extensive co-localization of caspase-3 and myosin labelling was found in the myocytes of both the heart and the slow-twitch soleus muscle. This, together with similar spatial distributions and responses to catecholamine doses, suggests that either caspase-3 activation occurs in necrotic as well as apoptotic myocytes or that a large proportion of apoptotic myocytes progress to secondary necrosis in vivo.