机构：[1]Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.广州中医药大学深圳医院深圳医学信息中心[2]Cardiac Signaling Center, Medical University of South Carolina, Charleston, SC 29425, USA.
The sarcolemmal ATP-sensitive K+ (sarcKATP) channel plays a cardioprotective role during stress. However, the role of the sarcKATP channel in the apoptosis of cardiomyocytes and association with mitochondrial calcium remains unclear. For this purpose, we developed a model of LPS-induced sepsis in neonatal rat cardiomyocytes (NRCs). The TUNEL assay was performed in order to detect the apoptosis of cardiac myocytes and the MTT assay was performed to determine cellular viability. Exposure to LPS significantly decreased the viability of the NRCs as well as the expression of Bcl-2, whereas it enhanced the activity and expression of the apoptosis-related proteins caspase-3 and Bax, respectively. The sarcKATP channel blocker, HMR-1098, increased the apoptosis of NRCs, whereas the specific sarcKATP channel opener, P-1075, reduced the apoptosis of NRCs. The mitochondrial calcium uniporter inhibitor ruthenium red (RR) partially inhibited the pro-apoptotic effect of HMR-1098. In order to confirm the role of the sarcKATP channel, we constructed a recombinant adenovirus vector carrying the sarcKATP channel mutant subunit Kir6.2AAA to inhibit the channel activity. Kir6.2AAA adenovirus infection in NRCs significantly aggravated the apoptosis of myocytes induced by LPS. Elucidating the regulatory mechanisms of the sarcKATP channel in apoptosis may facilitate the development of novel therapeutic targets and strategies for the management of sepsis and cardiac dysfunction.
基金：
This study was supported by the grants from the National
Natural Science Foundation of China (no. 81101450)
第一作者机构：[1]Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.[*1]Central Laboratory,Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, 1 Fuhua Road, Shenzhen, Guangdong 518033,P.R. China
通讯作者：
通讯机构：[1]Central Laboratory, Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518033, P.R. China.[*1]Central Laboratory,Shenzhen Hospital Affiliated to Guangzhou University of Traditional Chinese Medicine, 1 Fuhua Road, Shenzhen, Guangdong 518033,P.R. China
推荐引用方式(GB/T 7714)：
Zhang Xiaohui,Zhang Xiaohua,Xiong Yiqun,et al.Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis.[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2016,38(3):758-766.doi:10.3892/ijmm.2016.2664.
APA：
Zhang Xiaohui,Zhang Xiaohua,Xiong Yiqun,Xu Chaoying,Liu Xinliang...&Liu Wenhe.(2016).Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis..INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,38,(3)
MLA：
Zhang Xiaohui,et al."Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis.".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 38..3(2016):758-766
