Increased expression of the pro-apoptotic Bcl2 family member PUMA and apoptosis by the muscle regulatory transcription factor MyoD in response to a variety of stimuli
Increased expression of the pro-apoptotic Bcl2 family member PUMA and apoptosis by the muscle regulatory transcription factor MyoD in response to a variety of stimuli
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DOI：
10.1007/s10495-009-0428-5
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发表时间：
2010-01-01
期刊：
影响因子：
7.2
通讯作者：
Weyman, Crystal M.
中科院分区：
文献类型：
--
作者：
Harford, Terri J.;Shaltouki, Atossa;Weyman, Crystal M.
我们之前报道过MyoD的表达水平与血清停药诱导分化的骨骼肌母细胞亚群中发生的细胞凋亡水平相关。在此，我们证明MyoD的表达有助于肌母细胞和成纤维细胞对各种凋亡刺激的凋亡水平。具体来说，由于致癌Ras的表达，骨骼肌母细胞在分化和凋亡方面都存在缺陷，而MyoD的重新表达可以恢复它们在血清停药后进行分化和凋亡的能力。此外，使用表达雌激素受体MyoD融合蛋白的成纤维细胞系，我们已经确定，添加雌激素使这些成纤维细胞对血清停药或依托泊苷或thapsigargin治疗诱导的凋亡敏感。RNAi介导的23A2或C2C12成肌细胞MyoD的沉默使这些细胞对血清停药、依托泊苷或thapsigargin治疗诱导的凋亡具有抗性。最后，在成肌细胞和成纤维细胞中，MyoD介导的对这些不同刺激的凋亡反应的调节与促凋亡Bcl2家族成员PUMA的诱导水平相关。
We have previously reported that the level of MyoD expression correlates with the level of apoptosis that occurs in a subpopulation of skeletal myoblasts induced to differentiate by serum withdrawal. Herein we document that MyoD expression contributes to the level of apoptosis in myoblasts and fibroblasts in response to a variety of apoptotic stimuli. Specifically, re-expression of MyoD in skeletal myoblasts rendered defective for both differentiation and apoptosis by the expression of oncogenic Ras restores their ability to undergo both differentiation and apoptosis in response to serum withdrawal. Further, using a fibroblast cell line expressing an estrogen receptor:MyoD fusion protein, we have determined that addition of estrogen sensitizes these fibroblasts to apoptosis induced by serum withdrawal, or by treatment with etoposide or thapsigargin. RNAi mediated silencing of MyoD in either 23A2 or C2C12 myoblasts renders these cells resistant to apoptosis induced by serum withdrawal, or by treatment with etoposide or thapsigargin. Finally, MyoD mediated regulation of the apoptotic response to these various stimuli, in both myoblasts and fibroblasts, correlates with the level of induction of the pro-apoptotic Bcl2 family member PUMA.