頁籤選單縮合
題名 | Effect of Methoxychlor on Ca²⁺ Homeostasis and Apoptosis in HA59T Human Hepatoma Cells |
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作 者 | Horng, Chi-ting; Chou, Chiang-ting; Tseng, Hui-wen; Cheng, Jin-shiung; Chang, Hong-tai; Chang, Po-min; Chen, I-li; Hung, Ming-chi; Tsai, Yi-jen; Tsai, Peng-chih; Liang, Wei-zhe; Kuo, Chun-chi; Kuo, Daih-huang; Ho, Chin-man; Lin, Jia-rong; Shieh, Pochuen; Jan, Chung-ren; | 書刊名 | The Chinese Journal of Physiology |
卷期 | 58:1 2015.02[民104.02] |
頁次 | 頁1-8 |
分類號 | 415.536 |
關鍵詞 | Apoptosis; Ca²⁺; Hepatoma; Methoxychlor; |
語文 | 英文(English) |
英文摘要 | Methoxychlor, an organochlorine pesticide, is thought to be an endocrine disrupter that affects Ca2+ homeostasis and cell viability in different cell models. This study explored the action of methoxychlor on cytosolic free Ca2+ concentrations ([Ca2+]i ) and apoptosis in HA59T human hepatoma cells. Fura-2, a Ca2+-sensitive fluorescent dye, was applied to measure [Ca2+]i . Methoxychlor at concentrations of 0.1-1 µM caused a [Ca2+]i rise in a concentration-dependent manner. Removal of external Ca2+ abolished methoxychlor’s effect. Methoxychlor-induced Ca2+ influx was confirmed by Mn2+-induced quench of fura-2 fluorescence. Methoxychlor-induced Ca2+ entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. Methoxychlor killed cells at concentrations of 10-130 µM in a concentration-dependent fashion. Chelating of cytosolic Ca2+ with 1,2-bis(2-aminophenoxy) ethane-N,N,N’,N’-tetraacetic acid/AM (BAPTA/AM) did not prevent methoxychlor’s cytotoxicity. Methoxychlor (10 and 50 µM) induced apoptosis concentration-dependently as determined by using Annexin V/propidium iodide staining. Together, in HA59T cells, methoxychlor induced a [Ca2+]i rise by inducing Ca2+ entry via protein kinase C-sensitive Ca2+-permeable channels, without causing Ca2+ release from stores. Methoxychlor also induced apoptosis that was independent of [Ca2+]i rises. |
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