Aristolochic acid I targeted to adenine nucleotide translocator sensitizes mitochondrial permeability transition pore opening in vitro:a possible mechanism for toxicity of aristolochic acid I
会议名称：《第十五届国际药理学大会》
会议日期：2006年
学科分类：0710[理学-生物学] 07[理学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 090102[农学-作物遗传育种]
关 键 词：aristolochic acid (AA) MPT ANT
摘 要：正 Aristolochic acid （AA） is an extract derived from nature manshuriensis. To study the mechanism of nephrotoxicity and possible hepatotoxicity. fifty C57BL/6J mice were used to test LD50. HepG2 cell line was used to test the cellular toxicity and rat liver mitochondria was isolated to detect mitochondria function. The LD50 of AA in mice was 29mg/kg. Kidney and liver injury were shown by quantification of plasma transaminase activities and histological analysis. For the mitochondria study, a lower AA concentration （5 - 25uM） strongly induced cyclosporin A - sensitive mitochondrial swelling. AA promoted both calcium and GSH release from the matrix of isolated mitochondria. AA also decreased greatly the mitochondrial membrane potential （ΔΨm）. In addition. AA significantly inhibited mitochondrial adenine nucleotide translocator （ ANT）. This inhibition of ANT likely facilitates the AA - induced MPT pore opening which mimicked the effect of atractyloside. a specific inhibitor of ANT. induced clear mitochondrial swelling. It is suggested that inhibition of ANT may mediate, in part, the AA induced MPT pore opening, which may be an important mechanism for AA toxici-