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Alternative kynurenic acid synthesis routes studied in the rat cerebellum.
Blanco Ayala, Tonali; Lugo Huitrón, Rafael; Carmona Aparicio, Liliana; Ramírez Ortega, Daniela; González Esquivel, Dinora; Pedraza Chaverrí, José; Pérez de la Cruz, Gonzalo; Ríos, Camilo; Schwarcz, Robert; Pérez de la Cruz, Verónica.
Afiliação
  • Blanco Ayala T; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
  • Lugo Huitrón R; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
  • Carmona Aparicio L; Laboratorio de Neuroquímica, Instituto Nacional de Pediatría, S.S.A. México D.F., Mexico.
  • Ramírez Ortega D; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
  • González Esquivel D; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
  • Pedraza Chaverrí J; Facultad de Química, Departamento de Biología, Universidad Nacional Autónoma de México México D.F., Mexico.
  • Pérez de la Cruz G; Facultad de Ciencias, Departmento de Matemáticas, Universidad Nacional Autónoma de México México D.F., Mexico.
  • Ríos C; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
  • Schwarcz R; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine Baltimore, MD, USA.
  • Pérez de la Cruz V; Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, S.S.A. México D.F., Mexico.
Front Cell Neurosci ; 9: 178, 2015.
Article em En | MEDLINE | ID: mdl-26041992
Kynurenic acid (KYNA), an astrocyte-derived, endogenous antagonist of α7 nicotinic acetylcholine and excitatory amino acid receptors, regulates glutamatergic, GABAergic, cholinergic and dopaminergic neurotransmission in several regions of the rodent brain. Synthesis of KYNA in the brain and elsewhere is generally attributed to the enzymatic conversion of L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). However, alternative routes, including KYNA formation from D-kynurenine (D-KYN) by D-amino acid oxidase (DAAO) and the direct transformation of kynurenine to KYNA by reactive oxygen species (ROS), have been demonstrated in the rat brain. Using the rat cerebellum, a region of low KAT activity and high DAAO activity, the present experiments were designed to examine KYNA production from L-KYN or D-KYN by KAT and DAAO, respectively, and to investigate the effect of ROS on KYNA synthesis. In chemical combinatorial systems, both L-KYN and D-KYN interacted directly with peroxynitrite (ONOO(-)) and hydroxyl radicals (OH•), resulting in the formation of KYNA. In tissue homogenates, the non-specific KAT inhibitor aminooxyacetic acid (AOAA; 1 mM) reduced KYNA production from L-KYN and D-KYN by 85.1 ± 1.7% and 27.1 ± 4.5%, respectively. Addition of DAAO inhibitors (benzoic acid, kojic acid or 3-methylpyrazole-5-carboxylic acid; 5 µM each) attenuated KYNA formation from L-KYN and D-KYN by ~35% and ~66%, respectively. ONOO(-) (25 µM) potentiated KYNA production from both L-KYN and D-KYN, and these effects were reduced by DAAO inhibition. AOAA attenuated KYNA production from L-KYN + ONOO(-) but not from D-KYN + ONOO(-). In vivo, extracellular KYNA levels increased rapidly after perfusion of ONOO(-) and, more prominently, after subsequent perfusion with L-KYN or D-KYN (100 µM). Taken together, these results suggest that different mechanisms are involved in KYNA production in the rat cerebellum, and that, specifically, DAAO and ROS can function as alternative routes for KYNA production.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Cell Neurosci Ano de publicação: 2015 Tipo de documento: Article País de afiliação: México País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Front Cell Neurosci Ano de publicação: 2015 Tipo de documento: Article País de afiliação: México País de publicação: Suíça