Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons
Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons
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DOI：
10.1111/j.1471-4159.2005.02999.x
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发表时间：
2005-04-01
影响因子：
4.7
通讯作者：
Yoneda, Y
中科院分区：
文献类型：
--
作者：
Nakamichi, N;Kambe, Y;Yoneda, Y
在体外培养3或9天的皮层神经元（DIV）中，暴露于过氧化氢（H2 O2）导致细胞活力以浓度依赖性方式显著降低，浓度范围为10 μ M至1 mM，与6至24 h之间的持续时间无关。然而，H2 O2是更有效地降低细胞活力在皮层神经元培养9 DIV比在那些为3 DIV。丙酮酸是有效的，在防止神经元细胞死亡在1毫米，甚至当添加1-3小时后，加入过氧化氢。半定量RT-PCR和蛋白质印迹分析显示，显着更高的mRNA和蛋白质的表达为一个特定的单羧酸转运蛋白（MCT）在培养的神经元9 DIV比在3 DIV。MCT的特异性抑制剂显著减弱丙酮酸对培养9 DIV的神经元的保护作用，而对培养3 DIV的神经元的保护作用无明显影响。这些结果表明，H2 O2的脆弱性可能至少部分涉及特定MCT亚型的表达，负责丙酮酸在培养的大鼠皮层神经元细胞表面的双向运输。
In cortical neurons cultured for 3 or 9 days in vitro (DIV), exposure to hydrogen peroxide (H2O2) led to a marked decrease in cell viability in a concentration-dependent manner at a concentration range of 10 mu M to 1 mM irrespective of the duration between 6 and 24 h. However, H2O2 was more potent in decreasing cellular viability in cortical neurons cultured for 9 DIV than in those for 3 DIV. Pyruvate was effective in preventing the neuronal cell death at 1 mM even when added 1-3 h after the addition of H2O2. Semi-quantitative RT-PCR and western blotting analyses revealed significantly higher expression of both mRNA and protein for a particular monocarboxylate transporter (MCT) in neurons cultured for 9 DIV than in those for 3 DIV. A specific inhibitor of MCT significantly attenuated the neuroprotection by pyruvate in neurons cultured for 9 DIV, without markedly affecting that in neurons cultured for 3 DIV. These results suggest that vulnerability to H2O2 may at least in part involve expression of particular MCT isoforms responsible for the bi-directional transport of pyruvate across cell surfaces in cultured rat cortical neurons.