Hypoxia-Inducible Factor-1α (HIF-1α) Inhibition Impairs Retinoic Acid-Induced Differentiation in SH-SY5Y Neuroblastoma Cells, Leading to Reduced Neurite Length and Diminished Gene Expression Related to Cell Differentiation.

Autor: Brum PO; Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. pedro.ozorio.brum@univie.ac.at.; Max F. Perutz Labs, University of Vienna, Dr Bohr-Gasse 9, Room 4.510, 1030, Vienna, Austria. pedro.ozorio.brum@univie.ac.at., Viola GD; Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil., Saibro-Girardi C; Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Tiefensee-Ribeiro C; Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Brum MO; New York City, NY, USA., Gasparotto J; Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil., Krolow R; Laboratório de Programação Neurobiológica do Comportamento Alimentar, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Moreira JCF; Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil., Gelain DP; Departamento de Bioquímica, Centro de Estudos em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Jazyk: angličtina
Zdroj: Neurochemical research [Neurochem Res] 2022 Feb; Vol. 47 (2), pp. 409-421. Date of Electronic Publication: 2021 Sep 23.
DOI: 10.1007/s11064-021-03454-3
Abstrakt: Neuroblastoma is the most common extracranial solid tumour in childhood, originated from cells of the neural crest during the development of the Sympathetic Nervous System. Retinoids are vitamin-A derived differentiating agents utilised to avoid disease resurgence in high-risk neuroblastoma treatment. Several studies indicate that hypoxia-a common feature of the tumoural environment-is a key player in cell differentiation and proliferation. Hypoxia leads to the accumulation of the hypoxia-inducible factor-1α (HIF-1α). This work aims to investigate the effects of the selective inhibition of HIF-1α on the differentiation induced by retinoic acid in human neuroblastoma cells from the SH-SY5Y lineage to clarify its role in cell differentiation. Our results indicate that HIF-1α inhibition impairs RA-induced differentiation by reducing neuron-like phenotype and diminished immunolabeling and expression of differentiation markers. HIF1A is involved in Retinoic Acid (RA) induced differentiation in SH-SY5Y neuroblastoma cells. siRNA HIF1A gene silencing leads to a weaker response to RA, demonstrated by changes in the neuro-like phenotype and diminished expression of differentiation markers.
(© 2021. The Author(s).)
Databáze: MEDLINE
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