Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of A...Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schonlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca<sup>2+</sup>]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.展开更多
文摘Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schonlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca<sup>2+</sup>]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.
