- 著者
- Can-Zhao Liu Xiang-Yu Li Ren-Hong Du Min Gao Ming-Ming Ma Fei-Ya Li Er-Wen Huang Hong-Shuo Sun Guan-Lei Wang Yong-Yuan Guan
- 出版者
- 日本循環器学会
- 雑誌
- Circulation Journal (ISSN:13469843)
- 巻号頁・発行日
- pp.CJ-16-0793, (Released:2016-10-19)
- 参考文献数
- 41
- 被引用文献数
- 13
Background:Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl–current (ICl.vol) in vascular smooth muscle cells (VSMCs). However, it is still not clear whether and how ClC-3 is transported to cell membranes, resulting in alteration ofICl.vol.Methods and Results:Volume-regulated chloride current (ICl.vol) was recorded by whole-cell patch clamp recording, and Western blotting and co-immunoprecipitation were performed to examine protein expression and protein-protein interaction. Live cell imaging was used to observe ClC-3 transporting. The results showed that an overexpression of endophilin A2 could increaseICl.vol, while endophilin A2 knockdown decreasedICl.vol. In addition, the SH3 domain of endophilin A2 mediated its interaction with ClC-3 and promotes ClC-3 transportation from the cytoplasm to cell membranes. The regulation of ClC-3 channel activity was also verified in basilar arterial smooth muscle cells (BASMCs) isolated from endophilin A2 transgenic mice. Moreover, endophilin A2 increase VSMCs proliferation induced by endothelin-1 or hypo-osmolarity.Conclusions:The present study identified endophilin A2 as a ClC-3 channel partner, which serves as a new ClC-3 trafficking insight in regulatingICl.volin VSMCs. This study provides a new mechanism by which endophilin A2 regulates ClC-3 channel activity, and sheds light on how ClC-3 is transported to cell membranes to play its critical role as a chloride channel in VSMCs function, which may be involved in cardiovascular diseases.
- 著者
- Jie Hao Wei-Wei Li Hong Du Zhi-Fang Zhao Fan Liu Jing-Chao Lu Xiu-Chun Yang Wei Cui
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.64, no.6, pp.548-557, 2016-06-01 (Released:2016-06-01)
- 参考文献数
- 27
- 被引用文献数
- 5 31
How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen–glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R-induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca2+ overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (ΔΨm) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury.