Apoptosis coincident with the differentiation of skeletal myoblasts is delayed by caspase 3 inhibition and abrogated by MEK-independent constitutive Ras signaling
Apoptosis coincident with the differentiation of skeletal myoblasts is delayed by caspase 3 inhibition and abrogated by MEK-independent constitutive Ras signaling
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DOI：
10.1038/sj.cdd.4400930
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发表时间：
2002-02-01
影响因子：
12.4
通讯作者：
Weyman, CM
中科院分区：
文献类型：
--
作者：
Dee, K;Freer, M;Weyman, CM
我们发现在23A2骨骼肌细胞分化过程中，有30-35%的细胞凋亡。细胞分化和细胞凋亡均受细胞密度和时间变量的控制，且这两个变量呈负相关。在允许亲代23A2成肌细胞分化和凋亡的条件下，由组成性Ras信号传导导致分化缺陷的成肌细胞（A2:H-Ras成肌细胞）不会凋亡。这不仅仅是它们分化缺陷表型的结果，因为成肌细胞通过表达E1A （A2:E1A成肌细胞）导致分化缺陷，但仍然凋亡。虽然通过MEK的信号传导对增殖的亲本23A2成肌细胞的存活很重要，但通过MEK的构成性信号传导并不负责A2:H-Ras成肌细胞的存活。最后，我们证明了caspase 3是被激活的，并且caspase 3活性的药理抑制可以延迟细胞凋亡而不影响分化。在不影响分化的情况下消除细胞凋亡可能是提高成肌细胞移植治疗肌营养不良疗效的有效途径。
We demonstrate that during 23A2 skeletal myoblast differentiation, between 30-35% of the population apoptose. Both differentiation and apoptosis are controlled by the variables of cell density and time and these variables are inversely related. In response to conditions that permit both differentiation and apoptosis of parental 23A2 myoblasts, myoblasts rendered differentiation-defective by constitutive Ras signaling (A2:H-Ras myoblasts) do not apoptose. This is not merely a consequence of their differentiation-defective phenotype since myoblasts rendered differentiation-defective by expression of E1A (A2:E1A myoblasts) still apoptose. Although signaling through MEK is important to the survival of proliferating parental 23A2 myoblasts, constitutive signaling through MEK is not responsible for the survival of A2:H-Ras myoblasts. Finally, we demonstrate that caspase 3 is activated and that pharmacological inhibition of caspase 3 activity delays apoptosis without affecting differentiation. Abrogating apoptosis without affecting differentiation could be a useful approach to improve the efficacy of myoblast transfer in the treatment of muscular dystrophies.