The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle
The transcriptional coactivator PGC-1β drives the formation of oxidative type IIX fibers in skeletal muscle
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DOI：
10.1016/j.cmet.2006.12.003
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发表时间：
2007-01-01
期刊：
影响因子：
29
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Arany, Zoltan;Lebrasseur, Nathan;Spiegelman, Bruce M.
骨骼肌必须执行不同种类的工作，而不同类型的纤维已经进化来适应这些工作。以前的工作已经表明，转录辅助激活因子PGC-1α驱动I型和IIA型肌肉纤维的形成，这两种纤维是“慢抽动”和高度氧化的。我们在这里表明，PGC-1β的转基因表达在功能上类似于PGC-1α，但与PGC-1α不同，它导致明显的IN纤维的诱导，IN纤维是氧化的，但具有“快速抽动”的生物物理特性。PGC-1β共激活MEF2转录因子家族，刺激IIX肌球蛋白重链(MHC)启动子。PGC-1β转基因肌肉纤维富含线粒体，并具有高度的氧化性，至少部分原因是由于PGC-1β共同激活了ERRα和PPARα。因此，这些转基因动物可以比野生动物跑得更长，工作量更大。综上所述，这些数据表明，PGC-1β推动含有IIX MHC的高氧化纤维的形成。
Skeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1 alpha drives the formation of type I and IIA muscle fibers, which are "slow-twitch" and highly oxidative. We show here that transgenic expression of PGC-1 beta, a coactivator functionally similar to but distinct from PGC-1 alpha, causes a marked induction of IN fibers, which are oxidative but have "fast-twitch" biophysical properties. PGC-1 beta coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1 beta transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1 beta of ERR alpha and PPAR alpha. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1 beta drives the formation of highly oxidative fibers containing type IIX MHC.