Role of Calcium in NaF-induced Apoptosis in H9c2 Cardiomyocytes

• Main Authors: Meng-Chih Su, 蘇孟之
• Other Authors: Jiin-Cherng Yen
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/27460624742999741287

碩士 === 國立陽明大學 === 藥理學研究所 === 99 === Our laboratory has previously demonstrated that sodium fluoride (NaF) causes apoptosis of H9c2 cadiomyocytes through activation of the NADPH oxidase (NOX)-mediated mitogen-activated protein kinases (MAPKs) pathways. Since the increase of Ca2+ was recently shown to induce apoptotic cell death of H9c2 cardiomyocytes, this study was aimed to clarify whether NaF induces an immediate increase of cytosolic Ca2+ in H9c2 cells and to examine the role of Ca2+ in NaF-induced apoptosis of H9c2 cardiomyocytes. Pretreatment with verapamil (an L-type Ca2+ channel blocker) or 2-aminoethoxydiphenyl borate (2-APB; an IP3 receptor inhibitor) or verapamil plus 2-APB significantly attenuated NaF-induced suppression of cell survival rate. Verapamil and 2-APB inhibited the NaF-induced increase of NOX activity and ROS production. Verapamil and 2-APB also inhibited the increase of cleaved caspase-3 induced by NaF. Moreover, the NaF-induced phosphorylation of extracelluar signal-regulated kinase-1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK was decreased by pretreatment with verapamil or 2-APB or verapamil plus 2-APB. These results suggested that the increase of cytosolic Ca2+ may mediate NaF-induced apoptosis of H9c2 cardiomyocytes through NOX/ROS/MAPKs pathway. In addition, this study also found that NaF-induced increase of Ca2+ may induce Akt phosphorylation, and Akt may play a cytoprotective role against NaF-induced cytotoxicity of cardiomyocytes.