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Cytosolic Calcium Alteration and Cell Injury by Silica in Rat Hepatocytes
Cha, Seok Ho,Cha, Shin Woo,Ko, Chang Bo,Yu, Soung Roung,Kim, Hye Sun,Paik, Sang Gi 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-
The purpose of this study was to clarify the effect of silica on cytosolic free calcium mobilization and cell injury in primary cultured rat hepatocytes. Cytosolic free calcium concentration ([Ca^2+]_1) was measured employing calcium sensitive fluorescent dye, Fura-2/AM, and cell injury was evaluated by determination of cellular ATP contents. Silica increased [Ca^2+]_1 in a concentration-dependent manner in hepatocytes (10^-5∼10^-2 M). Silica caused a biphasic increase in [Ca^2+]_1 which was composed of an initial rapid rise and following sustained phase. Ca^2+ removal from the medium resulted in abolishment of initial and sustained phase of silica (10^-2 M)-induced [Ca^2+]_1 in hepatocytes. The pretreatment with nifedipine (1 μM) attenuated silica-induced [Ca^2+]_1 increases. Silica decreased cellular ATP content in a dose-dependent manner. This silica-induced cell injury was attenuated by the pretreatment with EGTA (100 μM) and nifedipine (1 μM). This study suggests that the elevation of [Ca^2+]_1 caused by silica may be due mainly to influx through a plasma membrane Ca^2+ channel and hepatotoxicity by silica relate with alteration of calcium homeostasis.