title: Gene Expression Profile of NF-κB, Nrf2, Glycolytic, and p53 Pathways During the SH-SY5Y Neuronal Differentiation Mediated by Retinoic Acid.
abstract: SH-SY5Y cells, a neuroblastoma cell line that is a well-established model system to study the initial phases of neuronal differentiation, have been used in studies to elucidate the mechanisms of neuronal differentiation. In the present study, we investigated alterations of gene expression in SH-SY5Y cells during neuronal differentiation mediated by retinoic acid (RA) treatment. We evaluated important pathways involving nuclear factor kappa B (NF-κB), nuclear E2-related factor 2 (Nrf2), glycolytic, and p53 during neuronal differentiation. We also investigated the involvement of reactive oxygen species (ROS) in modulating the gene expression profile of those pathways by antioxidant co-treatment with Trolox®, a hydrophilic analogue of α-tocopherol. We found that RA treatment increases levels of gene expression of NF-κB, glycolytic, and antioxidant pathway genes during neuronal differentiation of SH-SY5Y cells. We also found that ROS production induced by RA treatment in SH-SY5Y cells is involved in gene expression profile alterations, chiefly in NF-κB, and glycolytic pathways. Antioxidant co-treatment with Trolox® reversed the effects mediated by RA NF-κB, and glycolytic pathways gene expression. Interestingly, co-treatment with Trolox® did not reverse the effects in antioxidant gene expression mediated by RA in SH-SY5Y. To confirm neuronal differentiation, we quantified endogenous levels of tyrosine hydroxylase, a recognized marker of neuronal differentiation. Our data suggest that during neuronal differentiation mediated by RA, changes in profile gene expression of important pathways occur. These alterations are in part mediated by ROS production. Therefore, our results reinforce the importance in understanding the mechanism by which RA induces neuronal differentiation in SH-SY5Y cells, principally due this model being commonly used as a neuronal cell model in studies of neuronal pathologies.
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil. 00124262@ufrgs.br.|Departamento de Bioquímica, Instituto de Medicina Tropical, Universidade Federal do Rio Grande do Norte-UFRN, Avenida Senador Salgado Filho 3000, Cep 59078-900, Natal, Rio Grande do Norte, Brazil. 00124262@ufrgs.br.
authors.forename: Matheus Augusto
authors.initials: MA
authors.lastname: de Bittencourt Pasquali
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vitor Miranda
authors.initials: VM
authors.lastname: de Ramos
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Ricardo D Oliveira
authors.initials: RDO
authors.lastname: Albanus
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Alice
authors.initials: A
authors.lastname: Kunzler
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luis Henrinque Trentin
authors.initials: LHT
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica, Instituto de Medicina Tropical, Universidade Federal do Rio Grande do Norte-UFRN, Avenida Senador Salgado Filho 3000, Cep 59078-900, Natal, Rio Grande do Norte, Brazil.
authors.forename: Rodrigo Juliani Siqueira
authors.initials: RJS
authors.lastname: Dalmolin
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
authors.affiliation: Departamento de Informática Aplicada, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Bento Gonçalves 9500, Cep 91501-970, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Leila
authors.initials: L
authors.lastname: Ribeiro
authors.affiliation: Departamento de Informática Aplicada, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Bento Gonçalves 9500, Cep 91501-970, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Luigi
authors.initials: L
authors.lastname: Carro
authors.affiliation: Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos 2600, Cep 90035-003, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: José Cláudio Fonseca
authors.initials: JCF
authors.lastname: Moreira
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D016159:Tumor Suppressor Protein p53; D014212:Tretinoin
keywords: Neuroblastoma; Neuronal differentiation; Oxidative stress; Retinoic acid; SH-SY5Y cells