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

Publication date: Available online 2 July 2019Source: Neurochemistry InternationalAuthor(s): Cynthia Navarro-Mabarak, Irma Mitre-Aguilar, Rafael Camacho-Carranza, Clorinda Arias, Alejandro Zentella-Dehesa, Jesús Javier Espinosa-AguirreAbstractCytochrome 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 show...

Source: Neurochemistry International - July 2, 2019 Category: Neuroscience Source Type: research