title: Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice.
abstract: 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 17β-estradiol (E2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E2 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 E2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E2 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 E2-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 E2 in terms of phosphorylating RLC. Applying siRNA strategy in C2C12 cells, pRLC triggered by E2 was found to be mediated by estrogen receptor-β and the G protein-coupled estrogen receptor. Together, these results provide evidence that E2 modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females.
authors.affiliation: Programs in Rehabilitation Sciences and Physical Therapy, Department of Physical Medicine and Rehabilitation, Medical School, University of Minnesota, Minneapolis, Minnesota; College of Biological Engineering, Henan University of Technology, Zhengzhou, Henan, China; and.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Lai
authors.affiliation: Programs in Rehabilitation Sciences and Physical Therapy, Department of Physical Medicine and Rehabilitation, Medical School, University of Minnesota, Minneapolis, Minnesota;
authors.forename: Brittany C
authors.initials: BC
authors.lastname: Collins
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota;
authors.forename: Brett A
authors.initials: BA
authors.lastname: Colson
authors.affiliation: Institute of Gender in Medicine, Charite University Hospital, and German Centre for Cardiovascular Research (DZHK), Partner Site, Berlin, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kararigas
authors.affiliation: Programs in Rehabilitation Sciences and Physical Therapy, Department of Physical Medicine and Rehabilitation, Medical School, University of Minnesota, Minneapolis, Minnesota; lowex017@umn.edu.
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Lowe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D055785:Gene Knockdown Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D018994:Myosin Light Chains / Q000187:drug effects* / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015398:Signal Transduction
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004958:Estradiol; D047629:Estrogen Receptor beta; D004967:Estrogens; D020928:Mitogen-Activated Protein Kinases; D018994:Myosin Light Chains; D009219:Myosin-Light-Chain Kinase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C532507:GPER1 protein, mouse
keywords: RLC; estrogen; estrogen receptor; kinase; post tetanic potentiation