Differential effects of cytokines and redox potential on glutamate uptake in rat cortical glial cultures.
Perturbation of glutamate uptake may contribute to the pathogenesis of neuronal damage in the central nervous system. Cytokine overproduction, oxidative stress, energy failure, and metabolic impairment are commonly concomitant or resultant consequences of brain injury, which might synergistically exacerbate neuronal damage. In this study, we elucidate the effects of these events on glutamate uptake. Rat cortical glial cultures lowered the concentration of extracellular glutamate via glutamate transporters. Disturbance of ionic gradients, energy depletion, and reduced metabolic function impaired glutamate transporter activity. Tumor necrosis factor-alpha and interleukin (lL)-1beta potentiated glutamate-mediated oxidative stress and finally resulted in decrease in glutamate transporter activity. However, IL-4 and IL-10 exhibited no significant effects on both events. These results suggest that oxidative stress has a potential neurotoxicity by means of impairing glutamate transport into astrocytes.
Liao
S L
SL
Department of Education and Research, Taichung Veterans General Hospital, No. 160, Section 3, Taichung-Gang Road, Taichung 40705, Taiwan, ROC.
Chen
C J
CJ
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology*; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D016207:Cytokines; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid