Regulation of PGC-1α and PGC-1α-responsive genes with forskolin-induced Schwann cell differentiation
Regulation of PGC-1α and PGC-1α-responsive genes with forskolin-induced Schwann cell differentiation
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DOI：
10.1016/j.neulet.2008.04.104
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发表时间：
2008-07-18
影响因子：
2.5
通讯作者：
Russell, James W.
中科院分区：
文献类型：
--
作者：
Cowell, Rita M.;Blake, Kathryn R.;Russell, James W.
最近的证据表明，线粒体稳态对髓鞘形成和周围神经功能的维持至关重要。缺乏代谢转录辅助激活因子过氧化物酶体增殖物激活受体γ辅助激活因子1 α (PGC-1 α)的小鼠表现出髓鞘相关蛋白表达减少和髓鞘相关病变，因此我们在体外雪旺细胞（SCs）中鉴定了PGC-1 α靶基因，以确定PGC-1 α在胶质细胞中的潜在作用，并测试了PGC-1 α是否足以使SC分化和髓鞘形成。forskolin诱导的分化与PGC-1 α mRNA和蛋白的上调有关，虽然PGC-1 α的过表达上调了锰超氧化物歧化酶和雌激素相关受体α等基因，但不足以诱导分化。PGC-1 α过表达和forskolin暴露均引起线粒体融合相关蛋白mitofusin 1的增加。这些研究表明PGC-1 α可能是在分化和髓鞘形成过程中促进线粒体稳定性的潜在靶点。爱思唯尔爱尔兰有限公司出版。
Recent evidence indicates that mitochondrial homeostasis is critical for myelination and maintenance of peripheral nerve function. Mice lacking the metabolic transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1 alpha) show reductions in expression of myelin-related proteins and exhibit myelin-associated lesions, so we identified PGC-1 alpha target genes in Schwann cells (SCs) in vitro to determine potential roles for PGC-alpha in glia and tested whether PGC-1 alpha was sufficient for SC differentiation and myelination. Forskolin-induced differentiation was associated with an upregulation of PGC-1 alpha mRNA and protein, and while overexpression of PGC-1 alpha upregulated genes such as manganese superoxide dismutase and estrogen-related receptor alpha, it was not sufficient for induction of differentiation. Both PGC-1 alpha overexpression and forskolin exposure caused an increase in the mitochondrial fusion-related protein mitofusin 1. These studies suggest that PGC-1 alpha might be a potential target to promote mitochondrial stability during differentiation and myelination. Published by Elsevier Ireland Ltd.