Lipopolysaccharide sensitizes microglia toward Ca2+-induced cell death:: Mode of cell death shifts from apoptosis to necrosis
Lipopolysaccharide sensitizes microglia toward Ca2+-induced cell death:: Mode of cell death shifts from apoptosis to necrosis
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DOI：
10.1002/glia.20260
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发表时间：
2006-01-01
期刊：
影响因子：
6.2
通讯作者：
Takemura, M
中科院分区：
文献类型：
--
作者：
Nagano, T;Kimura, SH;Takemura, M
小胶质细胞激活对细胞死亡的影响知之甚少。本研究探讨了脂多糖（LPS）和干扰素-γ（IFN-γ），小胶质细胞激活的触发器，对细胞死亡诱导的几种药物在培养的大鼠小胶质细胞的影响。为了比较，还在培养的星形胶质细胞中检查LPS对细胞死亡的影响。LPS或IFN-γ增强了毒胡萝卜素或离子霉素诱导的细胞死亡，离子霉素是一种增加细胞内Ca 2+浓度的药物，尽管单独的LPS或IFN-γ不影响细胞活力。毒胡萝卜素或离子霉素诱导LPS处理的小胶质细胞凋亡，而它们诱导LPS处理的小胶质细胞坏死，其被O，O ′-双（2-氨基苯基）乙二醇-N，N，N ′，N ′-四乙酸四乙酰氧基甲酯（BAPTA-AM，一种细胞内Ca 2+螯合剂）部分逆转。相反，LPS处理不影响衣霉素或星形孢菌素诱导的细胞凋亡，而它抑制S-亚硝基-N-乙酰青霉胺诱导的细胞凋亡。在星形胶质细胞中未观察到脂多糖对毒胡萝卜素或离子霉素诱导的细胞凋亡的影响。这些结果表明，小胶质细胞活化的细胞对细胞内Ca 2+浓度的变化诱导的细胞死亡的敏感性和细胞死亡的模式从凋亡转移到坏死。(c)2005 Wiley-Liss，Inc.
Little is known about the effect of microglial activation on cell death. This study examines the effects of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), triggers of microglial activation, on cell death induced by several agents in cultured rat microglia. For comparison, the effect of LPS on cell death is also examined in cultured astrocytes. LPS or IFN--y enhanced cell death induced by thapsigargin or ionomycin, an agent that increases intracellular Ca2+ concentration, although LPS or IFN--y alone did not affect cell viability. Thapsigargin or ionomycin induced apoptosis in LPS-untreated microglia, while they induced necrosis in LPS-treated microglia, which were partially reversed by O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM, an intracellular Ca2+ chelator). In contrast, LPS treatment did not affect tunicamycin- or staurosporine-induced apoptosis, while it inhibited S-nitroso-N-acetylpenicillamine-induced apoptosis. The effect of LPS on thapsigargin or ionomycin-induced apoptosis was not observed in astrocytes. These results indicate that microglial activation sensitizes the cells toward cell death induced by the change in intracellular Ca2+ concentration and shifts the mode of cell death from apoptosis to necrosis. (c) 2005 Wiley-Liss, Inc.