Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice

Autor: Dawn A. Lowe, Shaojuan Lai, Brittany C. Collins, Brett A. Colson, Georgios Kararigas
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
Myosin Light Chains
Myosin light-chain kinase
Physiology
Ovariectomy
Endocrinology
Diabetes and Metabolism
Blotting
Western
Muscle Fibers
Skeletal
Biology
Cell Line
Receptors
G-Protein-Coupled
Contractility
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Physiology (medical)
Internal medicine
Ca2+/calmodulin-dependent protein kinase
Myosin
medicine
Animals
Estrogen Receptor beta
Phosphorylation
RNA
Small Interfering
Muscle
Skeletal
Myosin-Light-Chain Kinase
Protein kinase B
Estrogen receptor beta
Phosphoinositide-3 Kinase Inhibitors
Estradiol
Skeletal muscle
Estrogens
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Receptors
Estrogen
Gene Knockdown Techniques
Call for Papers
Female
Mitogen-Activated Protein Kinases
medicine.symptom
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Muscle Contraction
Signal Transduction
Muscle contraction
Zdroj: American Journal of Physiology-Endocrinology and Metabolism. 310:E724-E733
ISSN: 1522-1555
0193-1849
DOI: 10.1152/ajpendo.00439.2015
Popis: 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.
Databáze: OpenAIRE
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