Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice
Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice
复制标题
DOI：
10.1152/ajpendo.00439.2015
复制
发表时间：
2016-05-01
影响因子：
5.1
通讯作者：
Lowe, Dawn A.
中科院分区：
文献类型：
--
作者：
Lai, Shaojuan;Collins, Brittany C.;Lowe, Dawn A.
Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone's effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C2C12, pRLC was increased by 17 beta-estradiol (E-2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E-2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mice (Sham). The reduced pRLC in OVX muscle was reversed by in vivo E-2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E-2 treatment, demonstrating physiological consequence. Western blot of those muscles revealed that low PTP corresponded with low pRLC and higher PTP with greater pRLC. We aimed to elucidate signaling pathways affecting E-2-mediated pRLC using a kinase inhibitor library and C2C12 cells as well as a specific myosin light chain kinase inhibitor in muscles. PI3K/Akt, MAPK, and CamKII were identified as candidate kinases sensitive to E-2 in terms of phosphorylating RLC. Applying siRNA strategy in C2C12 cells, pRLC triggered by E-2 was found to be mediated by estrogen receptor-beta and the G protein-coupled estrogen receptor. Together, these results provide evidence that E-2 modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females.
