Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons

被引:42
作者
Nakamichi, N [1 ]
Kambe, Y [1 ]
Oikawa, H [1 ]
Ogura, M [1 ]
Takano, K [1 ]
Tamaki, K [1 ]
Inoue, M [1 ]
Hinoi, E [1 ]
Yoneda, Y [1 ]
机构
[1] Kanazawa Univ, Grad Sch Nat Sci & Technol, Div Pharmaceut Sci, Mol Pharmacol Lab, Kanazawa, Ishikawa 9201192, Japan
关键词
hydrogen peroxide; monocarboxylate transporters; neuroprotection; neurotoxicity; pyruvate;
D O I
10.1111/j.1471-4159.2005.02999.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:84 / 93
页数:10
相关论文
共 33 条
[1]   Pyruvate protection against β-amyloid-induced neuronal death:: Role of mitochondrial redox state [J].
Alvarez, G ;
Ramos, M ;
Ruiz, F ;
Satrústegui, J ;
Bogónez, E .
JOURNAL OF NEUROSCIENCE RESEARCH, 2003, 73 (02) :260-269
[2]   Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes [J].
Baud, O ;
Greene, AE ;
Li, JR ;
Wang, H ;
Volpe, JJ ;
Rosenberg, PA .
JOURNAL OF NEUROSCIENCE, 2004, 24 (07) :1531-1540
[3]   DOES IMPAIRMENT OF ENERGY-METABOLISM RESULT IN EXCITOTOXIC NEURONAL DEATH IN NEURODEGENERATIVE ILLNESSES [J].
BEAL, MF .
ANNALS OF NEUROLOGY, 1992, 31 (02) :119-130
[4]   A novel postsynaptic density protein:: the monocarboxylate transporter MCT2 is co-localized with δ-glutamate receptors in postsynaptic densities of parallel fiber-Purkinje cell synapses [J].
Bergersen, L ;
Wærhaug, O ;
Helm, J ;
Thomas, M ;
Laake, P ;
Davies, AJ ;
Wilson, MC ;
Halestrap, AP ;
Ottersen, OP .
EXPERIMENTAL BRAIN RESEARCH, 2001, 136 (04) :523-534
[5]  
Desagher S, 1996, J NEUROSCI, V16, P2553
[6]  
Desagher S, 1997, J NEUROSCI, V17, P9060
[7]   FRIEDREICHS ATAXIA - INTRAVENOUS PYRUVATE LOAD TO DEMONSTRATE A DEFECT IN PYRUVATE METABOLISM [J].
DIJKSTRA, U ;
GABREELS, F ;
JOOSTEN, E ;
WEVERS, R ;
LAMERS, K ;
DOESBURG, W ;
RENIER, W .
NEUROLOGY, 1984, 34 (11) :1493-1497
[8]   The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells [J].
Dimmer, KS ;
Friedrich, B ;
Lang, F ;
Deitmer, JW ;
Bröer, S .
BIOCHEMICAL JOURNAL, 2000, 350 :219-227
[9]   EFFECT OF STRIATAL CELLS ON INVITRO MATURATION OF MESENCEPHALIC DOPAMINERGIC-NEURONS GROWN IN SERUM-FREE CONDITIONS [J].
DIPORZIO, U ;
DAGUET, MC ;
GLOWINSKI, J ;
PROCHIANTZ, A .
NATURE, 1980, 288 (5789) :370-373
[10]  
Fenton H. J. H., 1894, J CHEM SOC, V65, P899, DOI DOI 10.1039/CT8946500899