分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Tang, Yinglong
Wang, Huiwen
Gu, Lei
Yang, Zhiguang
Wu, Yanyun
Yuan, Qi
Ji, Guangju
Wei, Bin
Tang, Yinglong
Guo, Yuting
Gu, Lei
Yang, Zhiguang
Zhao, Gang
Zhang, Qing
摘要： RNA binding protein is identified as an important mediator of aberrant alternative splicing in muscle atrophy. The altered splicing of calcium channels, such as ryanodine receptors (RyRs), plays an important role in impaired excitation-contraction (E-C) coupling in muscle atrophy; however, the regulatory mechanisms of ryanodine receptor 1 (RyR1) alternative splicing leading to skeletal muscle atrophy remains to be investigated. In this study we demonstrated that CUG binding protein 1 (CUG-BP1) was up-regulated and the alternative splicing of RyR1 ASI (exon70) was aberrant during the process of neurogenic muscle atrophy both in human patients and mouse models. The gain and loss of function experiments in vivo demonstrated that altered splicing pattern of RyR1 ASI was directly mediated by an up-regulated CUG-BP1 function. Furthermore, we found that CUG-BP1 affected the calcium release activity in single myofibers and the extent of atrophy was significantly reduced upon gene silencing of CUG-BP1 in atrophic muscle. These findings improve our understanding of calcium signaling related biological function of CUG-BP1 in muscle atrophy. Thus, we provide an intriguing perspective of involvement of mis-regulated RyR1 splicing in muscular disease.
分类： 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间： 2016-05-11
摘要： Calcium (Ca2+) oscillations play a central role in varieties of cellular processes including fertilization and immune response, but controversy over the regulation mechanisms still exists. It has been known that nitric oxide (NO) dependently regulates Ca2+ signaling in most physiopathological processes. Previous study indicated that eNOS translocation during some pathological process influences intracellular Ca2+ homeostasis. In this study, we investigated the role and mechanism of NO on Ca2+ release by overexpressing eNOS in cytoplasm (Cyto-eNOS) and endoplasmic reticulum (ER-eNOS) of HeLa cells. We found that the properties of Ca2+ release were altered by the overexpression of eNOS. The amplitude and frequency of extracellular ATP (eATP)-induced Ca2+ oscillation were enhanced in both Cyto-eNOS and ER-eNOS cells, respectively. Especially, the enhancement of the amplitude and frequency of the Ca2+ oscillation was much more significant in the ER-eNOS cells than that of Cyto-eNOS cells. Further study indicated that this effect was abrogated by NO inhibitor, 1..-NAME, suggesting it was not an artificial result induced by ER stress. Furthermore, an up-regulated phosphorylation of phospholamban (PLB) was observed and the sarco-endoplasmic reticulum Ca2tATPase (SERCA) function was activated followed by the significant increase in the ER Ca2+ load. Taken together, we revealed a novel regulatory mechanism of Ca2+ oscillation. (C) 2014 Elsevier Inc. All rights reserved.
点击量
待评议
点击量
下载量
评论
