title: δ-Aminolevulinate Dehydratase Activity is Stimulated in a MPTP Mouse Model of Parkinson's Disease: Correlation with Myeloperoxidase Activity.
abstract: Myeloperoxidase (MPO) is an inducible heme peroxidase responsive to some stress situations. It is already known that its activity is stimulated in neurodegenerative disorders and in the animal model of parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By contrast, the role of δ-aminolevulinate dehydratase (δ-ALA-D), an essential enzyme for heme synthesis, has not been investigated in the MPTP model. The aim of this study was to investigate the involvement of striatal δ-ALA-D activity in an acute model of PD, induced by MPTP, in C57Bl/6 mice and its correlation with MPO activity. Animals received four MPTP injections (20 mg/kg, i.p.) or saline (vehicle) to induce a PD model. 7 days after MPTP administration, the motor function was evaluated through rotarod and challenging beam tests in mice. Afterward, mice were killed, and the striata were removed for biochemical analyses. MPTP-treated mice showed impairment in motor skills, such as balance and motor coordination. Furthermore, there was a reduction of tyrosine hydroxylase levels in these animals, which characterizes the dopaminergic lesion. Striatal δ-ALA-D activity was stimulated by MPTP, as well as the MPO activity, and a significant positive correlation between δ-ALA-D and MPO activities was also demonstrated. These data suggest that δ-ALA-D activity could be stimulated due to the requirement of heme groups by peroxidases. Therefore, this study demonstrated for the first time the involvement of striatal δ-ALA-D activity in the MPTP model and its correlation with the MPO activity.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.
authors.forename: Tuane Bazanella
authors.initials: TB
authors.lastname: Sampaio
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.
authors.forename: Marcel Henrique
authors.initials: MH
authors.lastname: Marcondes Sari
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Pesarico
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil. criswn@ufsm.br.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism*; D000623:Porphobilinogen Synthase / Q000378:metabolism*
chemical_list: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D009195:Peroxidase; D000623:Porphobilinogen Synthase
keywords: Heme; MPTP; Myeloperoxidase; Parkinson’s disease; Peroxidase; δ-ALA-D