Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells
Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells
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DOI：
10.1016/s0891-5849(01)00591-3
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发表时间：
2001-08-01
影响因子：
7.4
通讯作者：
Hirano, S
中科院分区：
文献类型：
--
作者：
Anuradha, CD;Kanno, S;Hirano, S
已经表明氧化应激在各种形式的细胞死亡中起主要作用，包括坏死和凋亡。我们以前报道过氟化物（NaF）通过激活caspase-3诱导HL-60细胞凋亡。本研究的主要目的是探讨氟化钠诱导caspase-3上游细胞凋亡的可能途径，因为其机制尚不清楚。本研究表明，暴露于NaF后，有增加的MDA和4-HNE和线粒体膜电位（Δ Psi（m））的损失也观察到在NaF处理的细胞。有一个显着的增加，细胞色素c，这是从线粒体释放。我们已经报道了NaF处理的细胞中Bcl-2蛋白的下调。抗氧化剂N-乙酰半胱氨酸（NAC）、谷胱甘肽（GSH）保护细胞免于Δ Psi（m）的损失，并且没有细胞色素c退出或Bcl-2下调，我们认为这些抗氧化剂防止NaF诱导的细胞凋亡。这些结果表明，NaF可能通过氧化应激诱导的脂质过氧化作用诱导细胞凋亡，导致Δ Psi（m）的损失，从而将细胞色素c释放到细胞质中，并进一步触发caspase级联反应，导致HL-60细胞的凋亡性细胞死亡。(C)2001 Elsevier Science Inc.
It has been suggested that oxidative stress plays a major role in various forms of cell death, including necrosis and apoptosis. We have previously reported that fluoride (NaF) induces apoptosis in HL-60 cells by caspase-3 activation. The main focus of this investigation was to arrive at a possible pathway of the apoptosis induced by NaF upstream of caspase-3, because the mechanism is still unknown. The present study showed that after exposure to NaF, there was an increase in MDA and 4-HNE and a loss of mitochondrial membrane potential (delta Psi (m)) was also observed in NaF-treated cells. There was a significant increase in cytosolic cytochrome c, which is released from the mitochondria. We have reported a downregulation of Bcl-2 protein in NaF-treated cells. The antioxidants N-acetyl cysteine (NAC), glutathione (GSH) protected the cells from loss of delta Psi (m), and there was no cytochrome c exit or Bcl-2 downregulation, and we suggest that these antioxidants prevent apoptosis induced by NaF. These results suggested that perhaps NaF induced apoptosis by oxidative stress-induced lipid peroxidation, causing loss of delta Psi (m), and thereby releasing cytochrome c into the cytosol and further triggering the caspase cascade leading to apoptotic cell death in HL-60 cells. (C) 2001 Elsevier Science Inc.