Prolyl hydroxylase domain 2 deficiency promotes skeletal muscle fiber-type transition via a calcineurin/NFATc1-dependent pathway
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- 作者：Junchul Shin ; Aki Nunomiya ; Yasuo Kitajima ; Takashi Dan ; Toshio Miyata…
- 关键词：Hypoxia ; inducible factor α ; Prolyl hydroxylate domain protein 2 ; Type I muscle fiber ; Calcineurin ; NFATc1
- 刊名：Skeletal Muscle
- 出版年：2016
- 出版时间：December 2016
- 年：2016
- 卷：6
- 期：1
- 全文大小：2,796 KB
- 刊物主题：Cell Biology; Developmental Biology; Biochemistry, general; Systems Biology; Biotechnology;
- 出版者：BioMed Central
- ISSN：2044-5040
文摘
Background Hypoxia exposure is known to induce an alteration in skeletal muscle fiber-type distribution mediated by hypoxia-inducible factor (HIF)-α. The downstream pathway of HIF-α leading to fiber-type shift, however, has not been elucidated. The calcineurin pathway is one of the pathways responsible for slow muscle fiber transition. Because calcineurin pathway is activated by vascular endothelial growth factor (VEGF), one of the factors induced by HIF-1α, we hypothesized that the stabilization of HIF-1α may lead to slow muscle fiber transition via the activation of calcineurin pathway in skeletal muscles. To induce HIF-1α stabilization, we used a loss of function strategy to abrogate Prolyl hydroxylase domain protein (PHD) 2 responsible for HIF-1α hydroxylation making HIF-1α susceptible to ubiquitin dependent degradation by proteasome. The purpose of this study was therefore to examine the effect of HIF-1α stabilization in PHD2 conditional knockout mouse on skeletal muscle fiber-type transition and to elucidate the involvement of calcineurin pathway on muscle fiber-type transition.