期刊
JOURNAL OF NEUROCHEMISTRY
卷 93, 期 1, 页码 84-93出版社
WILEY
DOI: 10.1111/j.1471-4159.2005.02999.x
关键词
hydrogen peroxide; monocarboxylate transporters; neuroprotection; neurotoxicity; pyruvate
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.
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