Cell death-resistance of differentiated myotubes is associated with enhanced anti-apoptotic mechanisms compared to myoblasts.
Cell death-resistance of differentiated myotubes is associated with enhanced anti-apoptotic mechanisms compared to myoblasts.
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DOI：
10.1007/s10495-010-0566-9
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发表时间：
2011-03
期刊：
影响因子：
7.2
通讯作者：
Dupont-Versteegden, Esther E.
中科院分区：
文献类型：
--
作者：
Xiao, Rijin;Ferry, Amy L.;Dupont-Versteegden, Esther E.
骨骼肌萎缩与细胞凋亡升高有关，而肌肉分化导致细胞凋亡抵抗，表明细胞凋亡在骨骼肌中的作用是多方面的。本研究的目的是探讨增殖型成肌细胞与分化型肌管之间细胞凋亡易感性的机制，并假设分化型肌管中的细胞死亡抵抗是通过增强的抗凋亡通路介导的。用H2O2或Stsp处理C2C12成肌细胞和肌管，诱导细胞死亡。H2O2和Stsp诱导50%以上的成肌细胞DNA断裂，但在肌管中，只有不到10%的细胞核出现凋亡改变。H2O2和Stsp在成肌细胞中检测到线粒体膜电位耗散，而在肌管中这种反应大大减弱。与成肌细胞相比，肌管中的Caspase-3活性高10倍，Stsp在两者中都引起了显著的Caspase-3诱导。然而，暴露于H2O2并没有导致成肌细胞中caspase-3的激活，仅在肌管中有适度的诱导。caspase-2、-8和-9也有类似的反应。与成肌细胞相比，肌管中caspase抑制剂（凋亡抑制因子与caspase募集结构域（ARC））和热休克蛋白（HSP） 70和-25的丰度显著增加，此外，Stsp在肌管中抑制了ARC。此外，HSPs在成肌细胞中的表达增加，可减轻H2O2和Stsp对细胞死亡的影响。与成肌细胞相比，肌管中促凋亡蛋白内切酶G （EndoG）和凋亡诱导因子（AIF）的蛋白丰度更高。这些结果表明，尽管高水平的促凋亡信号机制，肌管对细胞凋亡的抗性仍增加，我们认为这种保护作用是通过增强的抗caspase机制介导的。
Skeletal muscle atrophy is associated with elevated apoptosis while muscle differentiation results in apoptosis resistance, indicating that the role of apoptosis in skeletal muscle is multifaceted. The objective of this study was to investigate mechanisms underlying apoptosis susceptibility in proliferating myoblasts compared to differentiated myotubes and we hypothesized that cell death-resistance in differentiated myotubes is mediated by enhanced anti-apoptotic pathways. C2C12 myoblasts and myotubes were treated with H2O2 or staurosporine (Stsp) to induce cell death. H2O2 and Stsp induced DNA fragmentation in more than 50% of myoblasts, but in myotubes less than 10% of nuclei showed apoptotic changes. Mitochondrial membrane potential dissipation was detected with H2O2 and Stsp in myoblasts, while this response was greatly diminished in myotubes. Caspase-3 activity was 10-fold higher in myotubes compared to myoblasts, and Stsp caused a significant caspase-3 induction in both. However, exposure to H2O2 did not lead to caspase-3 activation in myoblasts, and only to a modest induction in myotubes. A similar response was observed for caspase-2, -8 and -9. Abundance of caspase-inhibitors (apoptosis repressor with caspase recruitment domain (ARC), and heat shock protein (HSP) 70 and -25 was significantly higher in myotubes compared to myoblasts, and in addition ARC was suppressed in response to Stsp in myotubes. Moreover, increased expression of HSPs in myoblasts attenuated cell death in response to H2O2 and Stsp. Protein abundance of the pro-apoptotic protein endonuclease G (EndoG) and apoptosis-inducing factor (AIF) was higher in myotubes compared to myoblasts. These results show that resistance to apoptosis in myotubes is increased despite high levels of pro-apoptotic signaling mechanisms, and we suggest that this protective effect is mediated by enhanced anti-caspase mechanisms.
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影响因子：
4.8
作者：
Fernando, P;Brunette, S;Megeney, LA
通讯作者：
Megeney, LA
DOI：
10.1152/ajpregu.00458.2001
发表时间：
2002-02-01
影响因子：
2.8
作者：
Dirks, A;Leeuwenburgh, C
通讯作者：
Leeuwenburgh, C
DOI：
10.1152/ajpcell.1997.273.2.c579
发表时间：
1997-08-01
影响因子：
5.5
作者：
Allen, DL;Linderman, JK;Edgerton, VR
通讯作者：
Edgerton, VR
DOI：
10.1016/j.biocel.2006.07.009
发表时间：
2007-01-01
影响因子：
4
作者：
Camara, Yolanda;Duval, Carine;Villarroya, Francesc
通讯作者：
Villarroya, Francesc
影响因子：
64.8
作者：
Chun, HJ;Zheng, LX;Lenardo, MJ
通讯作者：
Lenardo, MJ