title: Signaling mechanisms underlying the glioprotective effects of resveratrol against mitochondrial dysfunction.
abstract: Resveratrol, a polyphenol found in grapes and red wine, exhibits antioxidant, anti-inflammatory, anti-aging and, neuroprotective effects. Resveratrol also plays a significant role modulating glial functionality, protecting the health of neuroglial cells against several neuropsychiatric in vivo and in vitro experimental models. Mitochondrial impairment strongly affected astrocyte functions and consequently brain homeostasis. Molecules that promote astrocyte mitochondrial protection are fundamental to maintain brain energy balance and cellular redox state, contributing to brain healthy. Thus, the present study was designed to evaluate some glioprotective mechanisms of resveratrol against mitochondrial damage promoted by azide exposure in hippocampal primary astrocyte cultures. Azide treatment provoked deleterious effects, including the dysfunction of mitochondria, the deterioration of redox homeostasis, the augmentation of pro-inflammatory cytokines and impairment of glutamate uptake activity. However, resveratrol prevented these effects, protecting hippocampal astrocytes against azide-induced cytotoxicity through the heme-oxygenase-1 (HO-1) pathway and inhibiting p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappa B (NFκB) activation. Resveratrol also protected astrocytes via phosphatidylinositide 3-kinase (PI3K)/Akt. These results contribute to the comprehension of the mechanisms by which resveratrol mediates hippocampal astrocyte protection against mitochondrial failure and implicate resveratrol as an important glioprotective molecule.
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: brunabellaver90@gmail.com.
authors.forename: Bruna
authors.initials: B
authors.lastname: Bellaver
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Larissa Daniele
authors.initials: LD
authors.lastname: Bobermin
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Débora Guerini
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Marília Danielly Nunes
authors.initials: MD
authors.lastname: Rodrigues
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Adriano Martimbianco
authors.initials: AM
authors.lastname: de Assis
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: andrequincozes@ufrgs.br.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000073039:Nitrosative Stress / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D019810:Sodium Azide / Q000633:toxicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D019810:Sodium Azide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D000077185:Resveratrol
keywords: Heme oxygenase-1 (HO-1); Hippocampal astrocytes; Mitochondrial dysfunction; Nuclear factor kappa B (NFκB); Resveratrol