title: PKCδ inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment.
abstract: The present study was designed to evaluate the specific role of protein kinase C (PKC) δ in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKCδ expression, while rottlerin, a PKCδ inhibitor, significantly attenuates MA-induced hyperthermia and behavioral deficits. These behavioral effects were not significantly observed in PKCδ antisense oligonucleotide (ASO)-treated- or PKCδ knockout (-/-)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKCδ (-/-)-mice. The administration of MA also results in a significant decrease of TH phosphorylation at ser 40, but not ser 31, while the inhibition of PKCδ consistently and significantly attenuates MA-induced reduction in the phosphorylation of TH at ser 40. Therefore, these results suggest that the MA-induced enhancement of PKCδ expression is a critical factor in the impairment of TH phosphorylation at ser 40 and that pharmacological or genetic inhibition of PKCδ may be protective against MA-induced dopaminergic neurotoxicity in vivo.
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Chu Xuan
authors.initials: CX
authors.lastname: Duong
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Xuan-Khanh Thi
authors.initials: XT
authors.lastname: Nguyen
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Bing
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Bach
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Dae Hun
authors.initials: DH
authors.lastname: Park
authors.affiliation: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Division of Neurotoxicology, National Center of Toxicological Research, FDA, Jefferson, Arkansas 72079, USA.
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.affiliation: Parkinson's Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Anumantha G
authors.initials: AG
authors.lastname: Kanthasamy
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, Baltimore, MD 21224, USA.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Cadet
authors.affiliation: Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya 468-8503, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D017931:DNA Primers; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D018345:Mice, Knockout; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D047428:Protein Kinase Inhibitors; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D051745:Protein Kinase C-delta