Author | Santana, Sânzio Silva | pt_BR |
Author | Pitanga, Thassila Nogueira | pt_BR |
Author | Santana, Jeanne Machado de | pt_BR |
Author | Zanette, Dalila Lucíola | pt_BR |
Author | Vieira, Jamile de Jesus | pt_BR |
Author | Yahouédéhou, Sètondji Cocou Modeste Alexandre | pt_BR |
Author | Adanho, Corynne Stephanie Ahouefa | pt_BR |
Author | Viana, Sayonara de Melo | pt_BR |
Author | Luz, Nivea Farias | pt_BR |
Author | Borges, Valeria de Matos | pt_BR |
Author | Goncalves, Marilda de Souza | pt_BR |
Access date | 2020-09-18T14:30:16Z | |
Available date | 2020-09-18T14:30:16Z | |
Document date | 2020 | |
Citation | SANTANA, Sânzio Silva et al. Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin. Frontiers in Immunology, v. 11, p. 1-12, 17 July 2020. | pt_BR |
ISSN | 1664-3224 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/43448 | |
Sponsorship | Brazilian National Council of Research (CNPq) (311888/2013-5) (MG) | pt_BR |
Sponsorship | MCD/CNPq/MS-SCTIE-DECIT (409800/2006-6) | pt_BR |
Sponsorship | Foundation for the Support of Research in the State of Bahia (FAPESB) (3626/2013, 1431040053063, and 9073/2007) | pt_BR |
Sponsorship | PPSUS/FAPESB (020/2013 EFP00007295) | pt_BR |
Sponsorship | Coordination for the Improvement of Higher Education Personnel (CAPES) agency–Finance Code 001 | pt_BR |
Language | eng | pt_BR |
Publisher | Frontiers Media | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Anemia falciforme | pt_BR |
Subject in Portuguese | Hidroxiureia | pt_BR |
Subject in Portuguese | Hemina | pt_BR |
Subject in Portuguese | Resposta antioxidante | pt_BR |
Subject in Portuguese | Nrf2 | pt_BR |
Title | Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin | en |
Type | Article | pt_BR |
DOI | 10.3389/fimmu.2020.01488 | pt_BR |
Abstract | The excessive release of heme during hemolysis contributes to the severity of sickle cell anemia (SCA) by exacerbating hemoglobin S (HbS) autoxidation, inflammation and systemic tissue damage. The present study investigated the effect of hydroxyurea (HU) on free radical neutralization and its stimulation of antioxidant genes in human peripheral blood mononuclear cells (PBMC) and human umbilical vein endothelial cells (HUVEC) in the presence or absence of hemin. HU (100 and 200µM) significantly reduced the production of intracellular reactive oxygen species (ROS) induced by hemin at 70µM in HUVEC. HUVECs treated with HU+hemin presented significant increases in nitric oxide (NO) production in culture supernatants. HU alone or in combination with hemin promoted the induction of superoxide dismutase-1 (SOD1) and glutathione disulfide-reductase (GSR) in HUVECs and PBMCs, and glutathione peroxidase (GPX1) in PBMCs. Microarray analysis performed in HUVECs indicated that HU induces increased expression of genes involved in the antioxidant response system: SOD2, GSR, microsomal glutathione S-transferase (MGST1), glutathione S transferase mu 2 (GSTM2), carbonyl reductase 1 (CBR1) and klotho B (KLB). Significant increases in expression were observed in genes with kinase activity: protein kinase C beta (PRKCB), zeta (PRKCZ) and phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta (PIK3C2B). HU also induced a significant increase in expression of the gene p62/sequestosome (p62/SQSTM1) and a significant decrease in the expression of the transcriptional factor BACH1 in HUVECs. Upstream analysis predicted the activation of Jun, miR-155-5p and mir-141-3p. These results suggest that HU directly scavenges free radicals and induces the expression of antioxidant genes via induction of the Nrf2 signaling pathway | en |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Católica do Salvador. Faculdade de Biomedicina. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Católica do Salvador. Faculdade de Biomedicina. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil. | pt_BR |
Subject | Sickle cell anemia | en |
Subject | Hydroxyurea | en |
Subject | Hemin | en |
Subject | Antioxidant response | en |
Subject | Nrf2 | pt_BR |
e-ISSN | 1664-3224 | pt_BR |