Time course of MPTP toxicity on translational control protein expression in mice brain.
The present study investigated in mice brain, the time course of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity on the expression of translational control proteins. Mice received intraperitoneal injections of MPTP (30 mg/kg/day) for 5 days and were sacrificed 1, 2, 3, 4 and 7 days after the last injection. The results, obtained by western blot, indicated that MPTP produced an alteration of the expression of proteins involved in the mTOR anti-apoptotic way and the PKR pro-apoptotic pathway of translational control especially in striatum and frontal cortex of mice. These disturbances were associated with a great activation of PKR in hippocampus at D9, the time point corresponding to maximal translational control alterations. Furthermore, whereas no modification of translational control protein expression was observed in mice substantia nigra after western blot procedure, immunofluorescent labeling revealed, in this target region of the toxin MPTP, a decrease of the expression of phospho-mTOR and a great activation of the phosphorylated form of PKR, marker of pathogenesis.
Deguil
Julie
J
Research Group on Brain Aging, GReViC, EA 3808, Pôle de Biologie Santé, 40 avenue du Recteur Pineau, 86022 POITIERS cedex, France.
Chavant
François
F
Lafay-Chebassier
Claire
C
Pérault-Pochat
Marie-Christine
MC
Fauconneau
Bernard
B
Pain
Stéphanie
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000633:toxicity*; D046188:Protein Modification, Translational / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013995:Time; D018675:Toxicity Tests; D019892:eIF-2 Kinase / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009498:Neurotoxins; C546843:mTOR protein, mouse; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D019892:eIF-2 Kinase