glutaminase and Manganese-Poisoning

The effects of manganese on the activities of GS, PAG, SDH and Na(+)-K(+)-ATPase were investigated and the impact of MK-801, Tau and DM on manganese-induced neurotoxicity were observed in rats. Seventy Wistar rats were divided into seven groups, 10 animals for each group. The first group was the control group, the second to fourth groups were 8, 40 and 200 micromol/kg MnCl(2) groups, the fifth to seventh groups were 0.3 micromol/kg MK-801, 1 micromol/kg Tau and 13.5 micromol/kg DM pretreatment groups. The animals were injected with manganese chloride for 25 days and pretreated for every other day. Manganese resulted in the reduction of GS, SDH and Na(+)-K(+)-ATPase activities, and the increase of PAG activity. The percentage of positive area and integral optical density of glutamate immunocreative cell were significantly increased in the group given 200 micromol/kg MnCl(2) alone. Pretreatment with MK-801, Tau and DM can antagonize neurotoxicity induced by manganese in the certain extent.

Topics: Animals; Cerebral Cortex; Chlorides; Corpus Striatum; Dextromethorphan; Dizocilpine Maleate; Dose-Response Relationship, Drug; Glutamate-Ammonia Ligase; Glutaminase; Hippocampus; Manganese Compounds; Manganese Poisoning; Neuroprotective Agents; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Taurine

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.

Topics: Animals; Blotting, Western; Chlorides; Corpus Striatum; Excitatory Amino Acid Transporter 1; Excitatory Amino Acid Transporter 2; Female; Glutamate-Ammonia Ligase; Glutamic Acid; Glutaminase; Glutamine; Male; Manganese; Manganese Compounds; Manganese Poisoning; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Riluzole; Sodium-Potassium-Exchanging ATPase