Role of NF-κB in cytochrome P450 epoxygenases down-regulation during an inflammatory process in astrocytes.

Autor: Navarro-Mabarak C; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico., Mitre-Aguilar IB; Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Av. Vasco de Quiroga Nº 15, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan, CP.14080, Ciudad de México, Mexico., Camacho-Carranza R; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, Mexico., Arias C; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico., Zentella-Dehesa A; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico; Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Av. Vasco de Quiroga Nº 15, Colonia Belisario Domínguez Sección XVI, Delegación Tlalpan, CP.14080, Ciudad de México, Mexico., Espinosa-Aguirre JJ; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico. Electronic address: jjea@biomedicas.unam.mx.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2019 Oct; Vol. 129, pp. 104499. Date of Electronic Publication: 2019 Jul 02.
DOI: 10.1016/j.neuint.2019.104499
Abstrakt: Cytochrome P450 (CYP) epoxygenases and their metabolic products, epoxyeicosatrienoic acids (EETs), have been proposed as important therapeutic targets in the brain. However, CYP expression can be modified by the presence of diverse pro-inflammatory cytokines and the subsequent activation of the NF-κB pathway. It has been indicated that CYP epoxygenases are down-regulated by inflammation in the heart, kidney and liver. However, up to this point, there has been no evidence regarding regulation of CYP epoxygenases during inflammation in the brain. Therefore, in order to explore the effects of inflammation and NF-κB activation in CYP2J3 and CYP2C11 regulation, rat primary astrocytes cultures were treated with LPS with and without IMD-0354 (selective NF-κB inhibitor). Cyp2j3 and Cyp2c11 mRNA expression was determined by qRT-PCR; protein expression was determined by immunofluorescence and by Western Blot and total epoxygenase activity was determined by the quantification of EETs by ELISA. NF-κB binding sites in Cyp2j3 and Cyp2c11 promoter regions were bioinformatically predicted and Electrophoretic Mobility Shift Assays (EMSA) were performed to determine if each hypothetic response element was able to bind NF-κB complexes. Results shown that LPS treatment is able to down-regulate astrocyte CYP2J3 and CYP2C11 mRNA, protein and activity. Additionally, we have identified NK-κB as the transcription factor involved in this regulation.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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