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	Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency
	Ono, K. ; Wang, X. F. ; Han, J. H. ; Han JH(韩家淮)
	2001
关键词	TRANSCRIPTION FACTOR MEF2 KAPPA-B ACTIVATION OXIDATIVE STRESS CYTOCHROME-C CATHEPSIN-D MITOCHONDRIAL CONTROL REGULATED SECRETION HEMATOPOIETIC-CELLS SERUM DEPRIVATION INDUCED APOPTOSIS
英文摘要	We used retrovirus insertion-mediated random mutagenesis to generate tumor necrosis factor (TNF)resistant lines from L929 cells. Using this approach, we discovered that the plasma membrane calcium ATPase 4 (PMCA4) is required for TNF-induced cell death in L929 cells. Under basal conditions, PMCA4-deficient (PMCA(mut)) cells have a normal phenotype. However, stimulation with TNF induces an abnormal increase in the intracellular calcium concentration ([Ca2+](i)). The substantially elevated [Ca2+](i) caused resistance to TNF-induced cell death. We found that an increase in the total volume of acidic compartments (VAC), mainly constituted by lysosomes, is a common event in cell death caused by a variety of agonists. The increased [Ca2+](i) in PMCA(mut) cells promoted lysosome exocytosis, which, at least in part, accounted for the inhibition of TNF-induced increase in VAC and cell death. Promoting lysosome exocytosis by calcium inhibited TNF-induced cell death in wild-type L929 cells, while inhibition of lysosome exocytosis or increase of VAC by sucrose restored the sensitivity of PMCA(mut) cells to TNF-induced cell death. Thus, increase of the volume of acidic compartment is a part of the cell death process, and the antideath effect of calcium is mediated, at least in part, by inhibition of the TNF-induced increase in VAC.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65880]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Ono, K.,Wang, X. F.,Han, J. H.,et al. Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency[J],2001.
APA	Ono, K.,Wang, X. F.,Han, J. H.,&韩家淮.(2001).Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency..
MLA	Ono, K.,et al."Resistance to tumor necrosis factor-induced cell death mediated by PMCA4 deficiency".(2001).

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