Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons.
In cortical neurons cultured for 3 or 9 days in vitro (DIV), exposure to hydrogen peroxide (H(2)O(2)) led to a marked decrease in cell viability in a concentration-dependent manner at a concentration range of 10 microm to 1 mm irrespective of the duration between 6 and 24 h. However, H(2)O(2) 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 H(2)O(2). 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 H(2)O(2) 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.
Nakamichi
Noritaka
N
Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kanazawa, Ishikawa, Japan.
Kambe
Yuki
Y
Oikawa
Hirotaka
H
Ogura
Masato
M
Takano
Katsura
K
Tamaki
Keisuke
K
Inoue
Maki
M
Hinoi
Eiichi
E
Yoneda
Yukio
Y
D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002247:Carbon Isotopes / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D000179:Acrylates; D001562:Benzimidazoles; D002247:Carbon Isotopes; D005904:Glial Fibrillary Acidic Protein; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; C043654:2-cyano-3-(1-phenylindol-3-yl)acrylate; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide; C017807:bisbenzimide ethoxide trihydrochloride