Proteomic characterization of the striatum and midbrain treated with 6-hydroxydopamine: alteration of 58-kDa glucose-regulated protein and C/EBP homologous protein.
The present study performed proteomic analysis of the midbrain and striatum of 6-hydroxydopamine (6-OHDA)-treated neonatal rats--a model of attention-deficit hyperactivity disorder (ADHD). Proteomic analysis revealed that a 58-kDa glucose-regulated protein (Grp58) was temporarily phosphorylated and its level was elevated by 6-OHDA. Furthermore, 6-OHDA increased the expression level of C/EBP homologous protein (CHOP), a mediator of endoplasmic reticulum (ER) stress response, in the midbrain and striatum. In vitro experiments using PC12 cells revealed that 6-OHDA or hydrogen peroxide could induce the elevation of Grp58 and CHOP. 6-OHDA could induce the elevation of Grp58 and CHOP in the presence of catalase, a hydrogen peroxide-removing enzyme, suggesting that the elevation of Grp58 and CHOP are induced by both hydrogen peroxide and p-quinone generated by 6-OHDA. Collectively, these findings suggest that ER stress involving the alteration of Grp58 and CHOP play a significant role in the induction of insults by 6-OHDA in vivo.
Akazawa
Yoko Ogawa
YO
Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Kansai Center, Ikeda, Osaka, Japan.
Saito
Yoshiro
Y
Nishio
Keiko
K
Horie
Masanori
M
Kinumi
Tomoya
T
Masuo
Yoshinori
Y
Yoshida
Yasukazu
Y
Ashida
Hitoshi
H
Niki
Etsuo
E
D000818:Animals; D000831:Animals, Newborn; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016227:Benzoquinones / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002853:Chromatography, Liquid; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism*; D015854:Up-Regulation
D016227:Benzoquinones; C497251:Ddit3 protein, rat; D051742:Transcription Factor CHOP; C004532:quinone; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D002374:Catalase; D020169:Caspases; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases; D004298:Dopamine