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首页> 外文期刊>The European Journal of Neuroscience >Pyruvate limits zinc-induced rat oligodendrocyte progenitor cell death.
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Pyruvate limits zinc-induced rat oligodendrocyte progenitor cell death.

机译：丙酮酸限制了锌诱导的大鼠少突胶质祖细胞死亡。

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摘要

A growing body of evidence suggests that excessive Zn2+ release plays a key role in inducing neuronal death during central nervous system injury. However, the possible cytotoxicity of extracellular Zn2+ to oligodendrocyte lineage cells remains unknown. Employing cultures of rat oligodendrocyte progenitor cells (OPC), we report here that OPC are vulnerable to increased extracellular Zn2+ levels and that pyruvate limits Zn2+-induced OPC death. Zn2+-induced concentration-dependent (pEC50 = -4.1 +/- 0.1) OPC death, which was insensitive to both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (Evans Blue) and l-type Ca2+ channel (nicardipine) inhibition. Neither kainate nor nicardipine influenced OPC 65Zn2+ accumulation, in contrast with the Zn2+ ionophore, pyrithione. Cytotoxic extracellular Zn2+ concentrations failed to increase OPC reactive oxygen species production and the antioxidant reagents, trolox, N,N'-diphenyl-1,4-phenylenediamine and N-tert-butyl-alpha-phenylnitrone did not afford significant protection from Zn2+ insults. The apoptotic inducer staurosporine induced the appearance of known apoptotic markers [pyknotic nuclei and caspase-3 specific (120 kDa) alpha-fodrin cleavage fragment], events not reproduced with Zn2+ insults. Zn2+ insults were also insensitive to the pan-caspase inhibitor Z-VAD-fmk. However, pyruvate afforded significant OPC protection from lethal Zn2+ insults. We conclude that cultured OPC are vulnerable to Zn2+ insults, via a nonoxidative stress and noncaspase-3-based mechanism, involving Zn2+ inhibition of OPC glycolysis.
机译：越来越多的证据表明，过量的Zn2 +释放在诱导中枢神经系统损伤期间神经元死亡中起关键作用。然而，细胞外Zn 2+对少突胶质细胞系细胞的可能细胞毒性仍然未知。利用大鼠少突胶质细胞祖细胞（OPC）的培养物，我们在这里报告说，OPC易受细胞外Zn2 +水平升高的影响，而丙酮酸限制了Zn2 +诱导的OPC死亡。 Zn2 +诱导的浓度依赖性（pEC50 = -4.1 +/- 0.1）OPC死亡，它对α-氨基-3-羟基-5-羟基-5-甲基-4-异恶唑丙酸受体（伊文思蓝）和l型Ca2 +均不敏感通道（尼卡地平）抑制。与Zn2 +离子载体，巯氧吡啶相比，海藻酸盐和尼卡地平均不影响OPC 65Zn2 +的积累。细胞毒性的细胞外Zn2 +浓度不能增加OPC活性氧的产生，抗氧化剂Troolox，N，N'-二苯基-1,4-苯二胺和N-叔丁基-α-苯基硝化氮不能提供有效的保护免受Zn2 +污染。凋亡诱导物星形孢菌素诱导了已知的凋亡标志物的出现[强固性核和caspase-3特异性（120 kDa）α-fodrin裂解片段]，但Zn2 +损伤并未产生该事件。 Zn2 +损伤也对泛半胱天冬酶抑制剂Z-VAD-fmk不敏感。然而，丙酮酸提供了对致命的Zn2 +伤害的显着OPC保护。我们得出的结论是，培养的OPC通过非氧化应激和基于noncaspase-3的机制（包括Zn2 +抑制OPC糖酵解）易受Zn2 +损伤。

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