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Antiarrhythmic Amiodarone Mediates Apoptotic Cell Death of HepG2 Hepatoblastoma Cells through the Mitochondrial Pathway


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タイトル: Antiarrhythmic Amiodarone Mediates Apoptotic Cell Death of HepG2 Hepatoblastoma Cells through the Mitochondrial Pathway
著者: Isomoto, Shojiro / Kawakami, Atsushi / Ohtsuru, Akira / Yamashita, Shunichi / Yano, Katsusuke
発行日: 2004年 6月
引用: Acta medica Nagasakiensia. 2004, 49(1-2), p.13-17
抄録: The antiarrhythmic amiodarone is known to cause hepatic toxicity. Recently, much attention has been devoted to the role of apoptosis in the pathogenesis of drug-induced cytotoxicity. The aim of this study is to investigate whether apoptosis contributes to hepatic toxicity caused by amiodarone and, if so, by which mechanism. HepG2 human hepatoblastoma cells were incubated for 48 hours with various concentration of amiodarone. To determine apoptotic cells, concentration of cytochrome c in the cytosol fraction, caspase-9 and -3 activities, and the percentage of the cells with hypodiploid DNA were measured quantitatively by flow cytometric assay or ELISA. The expression of Bcl-2-related proteins was examined by Western blot analysis. Amiodarone induced cytochrome c release into the cytosol fraction, activation of caspase-9 and caspase-3, and the occurrence of hypodiploid cells beginning at 10 μg/ml in the HepG2 cells. However, 2.5 μg/ml of amiodarone, a clinically attainable serum level, did not significantly. The expression of Bcl-xL but neither Bcl-2 nor Bax was decreased in the amiodarone-treated cells. Thus, amiodarone-induced cell death related with cytochrome c release and caspases in the HepG2 cells, suggesting that the drug causes hepatic toxicity in part through the induction of apoptosis. It is our conclusion that the amiodarone-induced apoptosis of HepG2 cells proceeds via the mitochondrial pathway, and is mediated by the downregulation of Bcl-xL.
キーワード: Apoptosis / Amiodarone / Hepatocytes / Caspase / Bcl-2
URI: http://hdl.handle.net/10069/9259
ISSN: 00016055
関連リンク : http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/49.13
資料タイプ: Departmental Bulletin Paper
原稿種類: publisher
出現コレクション:Volume 49, No. 1-2

引用URI : http://hdl.handle.net/10069/9259

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