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題名 | M-3M3FBS-Induced Ca²+ Movement and Apoptosis in HA59T Human Hepatoma Cells= |
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作者 | Liu, Shiuh-inn; Lin, Ko-long; Lu, Ti; Lu, Yi-chau; Hsu, Shu-shong; Tsai, Jeng-yu; Liao, Wei-chuan; Huang, Fong-dee; Chi, Chao-chuan; Liang, Wei-zhe; Tseng, Li-ling; Chiang, An-jen; Jan, Chung-ren; |
期刊 | The Chinese Journal of Physiology |
出版日期 | 20130200 |
卷期 | 56:1 2013.02[民102.02] |
頁次 | 頁26-35 |
分類號 | 415.138 |
語文 | eng |
關鍵詞 | Ca²+; m-3M3FBS; Hepatoma; Apoptosis; |
英文摘要 | The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca2+ concentrations ([Ca2+]i) in HA59T human hepatoma cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca2+]i levels in suspended cells by using fura-2 as a Ca2+-sensitive fluorescent dye. M-3M3FBS at concentrations of 10- 50 μM increased [Ca2+]i in a concentration-dependent fashion. The Ca2+ signal was reduced partly by removing extracellular Ca2+. M-3M3FBS-induced Ca2+ influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca2+-free medium, 50 μM m-3M3FBS pretreatment inhibited the [Ca2+]i rise induced by the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca2+]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca2+]i rise. At concentrations between 10 and 40 μM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca2+ with 1,2-bis(2- aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis in a concentration-dependent manner. M-3M3FBS also increased levels of reactive oxygen species. Together, in human hepatoma cells, m-3M3FBS induced a [Ca2+]i rise by inducing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via protein kinase C-sensitive store-operated Ca2+ channels. M-3M3FBS induced cell death that might involve apoptosis via mitochondrial pathways. |
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