Effects of arsenite on glutamate metabolism in primary cultured astrocytes.
The aim of this study was to explore the mechanisms that contribute to neurotoxicity induced by arsenite exposure focusing on the alteration of glutamate metabolism in primary cultured astrocytes. The cells were exposed to 0-30μM arsenite for 24h, and then cell viability, intracellular nonprotein sulfhydryl (NPSH) levels, mitochondrial membrane potential, activity of Na(+)/K(+)-ATPase, glutamine synthetase (GS) and glutamate transporter (GLAST and GLT-1), and protein expression of GS, GLAST and GLT-1 were examined. Compared with those in control, exposure to arsenite resulted in damages of astrocytes in a concentration dependent manner, which were shown by cell viabilities, and supported by morphological observation, mitochondrial membrane potential and intracellular NPSH levels. On the other hand, activities and protein expression of GS, GLAST and GLT-1 were significantly inhibited by arsenite exposure. Moreover, protein expression of GLAST and activities of GS were much more sensitive to arsenite. However, activities of Na(+)/K(+)-ATPase were not influenced obviously by arsenite exposure. In conclusion, findings from this study indicated that exposure to arsenite could inhibit glutamate metabolism in astrocytes, which might be related to arsenic-induced neurotoxicity.
Department of Environmental and Occupational Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Fenghong
F
Zhao
Yingjun
Y
Liao
Yaping
Y
Jin
Gexin
G
Li
Xiuqiang
X
Lv
Guifan
G
Sun
D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D018053:Arsenites; D004785:Environmental Pollutants; D027342:Excitatory Amino Acid Transporter 2; D013438:Sulfhydryl Compounds; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase; C015001:arsenite