Alteration of calcium signalling in cardiomyocyte induced by simulated microgravity and hypergravity.

Caizhi Liu,Shuai Liang,Xinxin Yuan,Yuheng Li,Yingxian Li,Youyou Li,Jianwei Li,Jianqi Xue,Zizhong Liu,Xiaoyan Jin,Jinping Song,Yingjun Tan,Dengchao Cao,Yuchen Yang,Yuezhang Zhou,Weijia Sun,Xingcheng Gao,Shukuan Ling,Guangming Zhong ,Ronghui Du ,Yang Zhao ,Di Zhao

doi:10.1111/cpr.12783

Abstract

ObjectivesCardiac Ca2+ signalling plays an essential role in regulating excitation‐contraction coupling and cardiac remodelling. However, the response of cardiomyocytes to simulated microgravity and hypergravity and the effects on Ca2+ signalling remain unknown. Here, we elucidate the mechanisms underlying the proliferation and remodelling of HL‐1 cardiomyocytes subjected to rotation‐simulated microgravity and 4G hypergravity.Materials and MethodsThe cardiomyocyte cell line HL‐1 was used in this study. A clinostat and centrifuge were used to study the effects of microgravity and hypergravity, respectively, on cells. Calcium signalling was detected with laser scanning confocal microscopy. Protein and mRNA levels were detected by Western blotting and real‐time PCR, respectively. Wheat germ agglutinin (WGA) staining was used to analyse cell size.ResultsOur data showed that spontaneous calcium oscillations and cytosolic calcium concentration are both increased in HL‐1 cells after simulated microgravity and 4G hypergravity. Increased cytosolic calcium leads to activation of calmodulin‐dependent protein kinase II/histone deacetylase 4 (CaMKII/HDAC4) signalling and upregulation of the foetal genes ANP and BNP, indicating cardiac remodelling. WGA staining indicated that cell size was decreased following rotation‐simulated microgravity and increased following 4G hypergravity. Moreover, HL‐1 cell proliferation was increased significantly under hypergravity but not rotation‐simulated microgravity.ConclusionsOur study demonstrates for the first time that Ca2+/CaMKII/HDAC4 signalling plays a pivotal role in myocardial remodelling under rotation‐simulated microgravity and hypergravity.

Highlights

Altered gravity conditions, such as micro- and hypergravity, have different effects on living beings at various levels of organization, including changing the biophysical properties of a single cell up to the level of the entire organism.[1-5]
This study showed that simulated microgravity and hypergravity could alter calcium signalling in cardiomyocytes
Spontaneous calcium oscillations and the cytosolic calcium concentration were both increased in HL-1 cells after simulated microgravity and 4G hypergravity

Summary

| INTRODUCTION

Altered gravity conditions, such as micro- and hypergravity, have different effects on living beings at various levels of organization, including changing the biophysical properties of a single cell up to the level of the entire organism.[1-5]. Ca2+ functions through the Ca2+ binding protein calmodulin (CaM) to activate CaMKII, which is activated by different pathological processes in the heart This Ca2+-CaMKIIdependent gene regulation during cardiac remodelling suggests novel strategies for Ca2+-CaMKII-dependent “transcriptional therapies” to control cardiac gene expression and function.[9]. HU of rats impaired the function of L-type Ca2+ channels and decreased intracellular Ca2+ ([Ca2+]i) transients, resulting in reduced responsiveness to β-adrenoceptor stimulation, which may be partially responsible for the decline in cardiac function These studies demonstrated that microgravity-induced changes in Ca2+ signalling play an important role in cardiac remodelling and reduced function. The changes in intracellular calcium signalling, and its regulatory role in cardiac remodelling under altered gravity, are not fully understood. We report that calcium signalling plays a pivotal role in regulating gravity alteration-induced cardiac remodelling through the Ca2+/CaMKII/HDAC4 signalling pathway

| MATERIALS AND METHODS

Findings

| DISCUSSION