Activation of mitochondrial-driven apoptosis in skeletal muscle cells is not mediated by reactive oxygen species production
Activation of mitochondrial-driven apoptosis in skeletal muscle cells is not mediated by reactive oxygen species production
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DOI：
10.1016/j.biocel.2006.07.009
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Villarroya, Francesc
中科院分区：
文献类型：
--
作者：
Camara, Yolanda;Duval, Carine;Villarroya, Francesc
虽然细胞凋亡抗性的获得是骨骼肌细胞分化程序的一部分，但分化的肌细胞可响应生理或病理刺激而经历细胞凋亡。由线粒体产生的活性氧在许多细胞类型的凋亡控制中起主要作用。事实上，它们参与控制分化的肌细胞的凋亡，或产生对凋亡的抗性仍然是未知的。此外，分化的肌细胞特异性表达解偶联蛋白-3，这是一种可能参与控制活性氧产生的线粒体蛋白。为了研究线粒体活性氧在骨骼肌细胞凋亡控制中的作用，将L 6 E9成肌细胞和肌管暴露于星形孢菌素（staurosporine），星形孢菌素是通过线粒体途径的凋亡诱导剂。星形孢菌素激活凋亡途径（即半胱天冬酶-3和半胱天冬酶-9），增加成肌细胞中的活性氧，并在较小程度上增加肌管中的活性氧。然而，活性氧的增加并不需要诱导细胞凋亡，也不参与成肌细胞和肌管对细胞凋亡的差异敏感性。此外，解偶联蛋白-3在肌管中的表达并不影响活性氧的产生，尽管它对星形孢菌素诱导的细胞凋亡产生轻微的致敏作用。结果表明，骨骼肌细胞中的凋亡激活主要涉及活性氧物种的独立机制和线粒体解偶联蛋白-3是不保护的活性氧物种的生产或肌细胞中的凋亡激活。(c)2006爱思唯尔有限公司保留所有权利。
While the acquisition of apoptosis resistance is part of the differentiation program of skeletal muscle cells, differentiated muscle cells can undergo apoptosis in response to physiological or pathological stimuli. The generation of reactive oxygen species by mitochondria plays a major role in the control of apoptosis in many cell types. Indeed their involvement in controlling apoptosis in differentiated muscle cells, or in generating resistance to apoptosis remains unknown. Moreover, differentiated muscle cells specifically express the uncoupling protein-3, a mitochondrial protein potentially involved in controlling reactive oxygen species production. To study the role of mitochondrial reactive oxygen species in the control of apoptosis in skeletal muscle cells, L6E9 myoblasts and myotubes were exposed to staurosporine, an inducer of apoptosis via mitochondrial pathways. Staurosporine activated apoptotic pathways (i.e. caspase-3 and caspase-9) increasing reactive oxygen species in myoblasts and, to a minor extent, in myotubes. However, the increase in reactive oxygen species was not needed to induce apoptosis nor was it involved in the differential sensitization of myoblasts and myotubes to apoptosis. Moreover, expression of uncoupling protein-3 in myotubes did not affect reactive oxygen species production, although it produced a slight sensitization for staurosporine-induced apoptosis. Results indicate that apoptotic activation in skeletal muscle cells mainly involves reactive oxygen species-independent mechanisms and that mitochondrial uncoupling protein-3 is not protective either for reactive oxygen species production or for apoptotic activation in muscle cells. (c) 2006 Elsevier Ltd. All rights reserved.