title: Induction of ferroxidase enzymatic activity by copper reduces MPP+-evoked neurotoxicity in rats.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by decreased dopamine, intracellular inclusions (Lewy bodies) and brain iron deposits. PD has also been related with reduced ferroxidase activity, diminished antioxidant defenses and lipid peroxidation. Striatal injection of 1-methyl-4-phenylpyridinium (MPP(+)) into rodents reproduces the major biochemical characteristics of PD, including oxidative stress. Copper (Cu) plays an important role as prosthetic group of several proteins involved in iron metabolism and antioxidant responses, such as ceruloplasmin (Cp). In the present study, intraperitoneal CuSO4 injection (10μmol/kg) produced an insignificant increase of Cu content in striatum and midbrain (17.5% and 7%, respectively). After 10 and 11h, Cu induced 6- and 4-fold increase Cp mRNA in midbrain and striatum, respectively. Cu-supplement also produced a time-dependent increase ferroxidase activity in striatal tissue, reaching a maximum 16h after Cu treatment in midbrain; while, ferrous iron content diminished 18% in striatum and 8% in midbrain. In regard the PD model, we found that MPP(+) (10μg/8μL, intrastriatal), induced a significant (P<0.05) reduction of striatal ferroxidase activity; this effect was reverted by Cu pre-treatment 16h before MPP(+). Likewise, Cu-supplement prevented lipid fluorescent products formation in striatum, evaluated (P<0.01) 6h after MPP(+). In the long term, apomorphine-evoked circling behavior was evaluated 6 days after MPP(+) injury; Cu pre-treatment significantly reduced (P<0.05) the apomorphine-induced ipsilateral turns in MPP(+)-lesioned rats. These results suggest that Cu-induced expression of Cp could be an interesting scope against the deleterious effects of iron deposits in PD.
authors.affiliation: Laboratorio de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suárez, Mexico.
authors.forename: Moisés
authors.initials: M
authors.lastname: Rubio-Osornio
authors.forename: Sergio
authors.initials: S
authors.lastname: Montes
authors.forename: Yessica
authors.initials: Y
authors.lastname: Heras-Romero
authors.forename: Jorge
authors.initials: J
authors.lastname: Guevara
authors.forename: Carmen
authors.initials: C
authors.lastname: Rubio
authors.forename: Penélope
authors.initials: P
authors.lastname: Aguilera
authors.forename: Susana
authors.initials: S
authors.lastname: Rivera-Mancia
authors.forename: Esaú
authors.initials: E
authors.lastname: Floriano-Sánchez
authors.forename: Antonio
authors.initials: A
authors.lastname: Monroy-Noyola
authors.forename: Camilo
authors.initials: C
authors.lastname: Ríos
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism*; D003300:Copper / Q000493:pharmacokinetics / Q000494:pharmacology*; D019327:Copper Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D010300:Parkinson Disease / Q000178:diet therapy / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003300:Copper; D002570:Ceruloplasmin; D019327:Copper Sulfate; D015655:1-Methyl-4-phenylpyridinium