Slow increase in intranuclear and cytosolic free calcium concentrations in L929 cells is important in tumour necrosis factor-alpha-mediated cell death
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摘要The potential involvement of cellular calcium in the signalling pathway of tumour necrosis factor-alpha (TNF) was assessed in L929 cells using Ca-45(2+) and confocal laser scanning microscopy with fluorescence calcium indicators. Our data indicate that the effect of TNF on intracellular Ca2+ mobilization is a slow process with no discernible increase in the cytosolic free Ca2+ concentration ([Ca2+]c) and intranuclear Ca2+ level ([Ca2+]n) within the 1st min of TNF (25 ng/ml) administration. However, prolonged exposure (2 h) of L929 cells to TNF brought about pronounced increase in cytosolic and intranuclear [Ca2+] even in the absence of external Ca2+. The increase in intracellular [Ca2+] was more apparent when cells were treated with thapsigargin, an inhibitor of microsomal Ca2+-ATPase. Interestingly, most of the Ca2+ released was around and confined to the nucleus. Following the pretreatment of cells with thapsigargin, a synergistic killing effect was obtained when cells were cultured with TNF. The use of Ca-45(2+) also revealed that TNF enhanced the Ca-45(2+) uptake in a time-dependent manner. Calcium channel blockers, verapamil and diltiazem, could alleviate both the TNF-mediated Ca-45(2+)- uptake and killing activity. Our results therefore suggest that an increase in cellular Ca2+ is a crucial factor in the TNF cytotoxicity.
著者Kong SK, Fung KP, Choy YM, Lee CY
期刊名稱Oncology
出版年份1997
月份1
日期1
卷號54
期次1
出版社KARGER
頁次55 - 62
國際標準期刊號0030-2414
語言英式英語
關鍵詞cellular calcium; confocal microscopy; fluorescence imaging; tumour necrosis factor-alpha
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-05-08 於 05:42