%0 Journal Article
%T Acute Skeletal Muscle Contractions Orchestrate Signaling Mechanisms to Trigger Nuclear NFATc1 Shuttling and Epigenetic Histone Modifications.
%A Suhr F
%A Braun K
%A Vanmunster M
%A Bloch W
%J Cell Physiol Biochem
%V 52
%N 3
%D 2019
%M 30907990
暂无%R 10.33594/000000045
%X <B>OBJECTIVE: </B>Calcium (Ca²⁺) coordinates skeletal muscle functions by controlling contractions as well as signaling pathways and transcriptional properties. The ryanodine receptor 1 (RyR1), its phosphorylation site (pRyR1Ser²⁸⁴⁰) and its stabilizers navigate Ca²⁺ oscillations to command muscle signaling cascades and transcriptional activities. While chronic exercise increases pRyR1Ser²⁸⁴⁰, investigations on acute exercise's effects on RyR1 and Ca²⁺-dependent modifications of skeletal muscle are rare. The aim of this study was to examine molecular events leading to RyR1 phosphorylation in a physiological model of acute exercise. We hypothesized that exercise-induced RyR1 phosphorylation is associated with altered Ca²⁺-dependent physiological phenotypes.<BR><B>METHODS: </B>We analyzed pRyR1Ser²⁸⁴⁰, its stabilizers, involved signaling pathways, and Ca²⁺-sensitive muscle-determining factors (i.e. NFATc1 and epigenetic histone H3 modifications) in rat muscles upon one single running bout of either concentric or eccentric contractions.<BR><B>RESULTS: </B>Both acute exercises significantly increased pRyRSer²⁸⁴⁰ levels in muscles, which was accompanied by dissociations of stabilizers from RyR1. Additionally, RyR1 phosphorylation-inducing signaling cascades PTEN/CaMKII/ PKA were significantly activated upon exercise. Further, RyR1 phosphorylations were associated with increased Ca²⁺-dependent NFATc1 nuclear abundances as well as increased Ca²⁺-dependent epigenetic H3 acetylations pointing to a pRyR1Ser²⁸⁴⁰-dependent rapid and novel Ca²⁺ equilibrium upon exercise.<BR><B>CONCLUSIONS: </B>Our data report synergistic actions of several distinct pathways to modify RyR1 function to govern physiological phenotypes, here expressed as increased nuclear NFATc1 abundances and epigenetic H3 modifications.