The protective effect of riluzole on manganese caused disruption of glutamate-glutamine cycle in rats.
The mechanisms underlying the disruption of glutamate-glutamine cycle (Glu-Gln cycle) in manganism are still unknown. To approach the concrete mechanisms, the rats were i.p. injected with different doses of MnCl(2) (0, 8, 40, and 200 micromol/kg), and the levels of Mn, Glu, and Gln, the morphological and ultrastructural changes, activities of Na(+)-K(+)-ATPase, GS, and PAG, mRNA and protein expression of GS, GLAST, and GLT-1 in the striatum were investigated. In addition, the effect of 21.35 micromol/kg riluzole (Na(+) channel blocker) was studied at 200 micromol/kg MnCl(2). It was observed that (1) Mn and Glu levels and PAG activity increased; (2) many pathological changes occurred; (3) Gln levels, Na(+)-K(+)-ATPase and GS activities, and GS, GLAST, and GLT-1 mRNA and protein expression inhibited, does dependently. Furthermore, the research indicated that pretreatment of riluzole reversed toxic effects of MnCl(2) significantly. These results suggested that Glu-Gln cycle was disrupted by Mn exposure dose dependently; riluzole might antagonize Mn neurotoxicity.
Deng
Yu
Y
Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110001, People's Republic of China.
Xu
Zhaofa
Z
Xu
Bin
B
Tian
Yawen
Y
Xin
Xin
X
Deng
Xiaoqiang
X
Gao
Jian
J
D000818:Animals; D015153:Blotting, Western; D002712:Chlorides / Q000633:toxicity*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D017895:Manganese Compounds; D020149:Manganese Poisoning / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019782:Riluzole / Q000378:metabolism / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002712:Chlorides; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D017895:Manganese Compounds; D018696:Neuroprotective Agents; C493392:Slc1a3 protein, rat; D005973:Glutamine; D018698:Glutamic Acid; D008345:Manganese; D019782:Riluzole; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; D000254:Sodium-Potassium-Exchanging ATPase; C025340:manganese chloride