Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/43448 |
Resumo: | Brazilian National Council of Research (CNPq) (311888/2013-5) (MG) |
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Santana, Sânzio SilvaPitanga, Thassila NogueiraSantana, Jeanne Machado deZanette, Dalila LucíolaVieira, Jamile de JesusYahouédéhou, Sètondji Cocou Modeste AlexandreAdanho, Corynne Stephanie AhouefaViana, Sayonara de MeloLuz, Nivea FariasBorges, Valeria de MatosGoncalves, Marilda de Souza2020-09-18T14:30:16Z2020-09-18T14:30:16Z2020SANTANA, 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 2020.1664-3224https://www.arca.fiocruz.br/handle/icict/4344810.3389/fimmu.2020.014881664-3224Brazilian National Council of Research (CNPq) (311888/2013-5) (MG)MCD/CNPq/MS-SCTIE-DECIT (409800/2006-6)Foundation for the Support of Research in the State of Bahia (FAPESB) (3626/2013, 1431040053063, and 9073/2007)PPSUS/FAPESB (020/2013 EFP00007295)Coordination for the Improvement of Higher Education Personnel (CAPES) agency–Finance Code 001Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Católica do Salvador. Faculdade de Biomedicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Católica do Salvador. Faculdade de Biomedicina. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, Brasil.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 pathwayengFrontiers MediaAnemia falciformeHidroxiureiaHeminaResposta antioxidanteNrf2Sickle cell anemiaHydroxyureaHeminAntioxidant responseNrf2Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/43448/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSantana, Sânzio Silva Hydroxyurea....pdfSantana, Sânzio Silva Hydroxyurea....pdfapplication/pdf3141232https://www.arca.fiocruz.br/bitstream/icict/43448/2/Santana%2c%20S%c3%a2nzio%20Silva%20Hydroxyurea....pdf21b33c0d20d5922886b57617a0b41527MD52Data_Sheet_1_Hydroxyurea Scavenges Free Radicals and Induces the Expression of Antioxidant Genes in Human Cell Cultures Treated With Hemin.pdfData_Sheet_1_Hydroxyurea Scavenges Free Radicals and Induces the Expression of Antioxidant Genes in Human Cell Cultures Treated With Hemin.pdfSupplementary Dataapplication/pdf486923https://www.arca.fiocruz.br/bitstream/icict/43448/4/Data_Sheet_1_Hydroxyurea%20Scavenges%20Free%20Radicals%20and%20Induces%20the%20Expression%20of%20Antioxidant%20Genes%20in%20Human%20Cell%20Cultures%20Treated%20With%20Hemin.pdf8a8e0e2c47b2a4d0e74d6f70f47598a6MD54TEXTSantana, Sânzio Silva Hydroxyurea....pdf.txtSantana, Sânzio Silva Hydroxyurea....pdf.txtExtracted 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| dc.title.en.fl_str_mv |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| title |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| spellingShingle |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin Santana, Sânzio Silva Anemia falciforme Hidroxiureia Hemina Resposta antioxidante Nrf2 Sickle cell anemia Hydroxyurea Hemin Antioxidant response Nrf2 |
| title_short |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| title_full |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| title_fullStr |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| title_full_unstemmed |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| title_sort |
Hydroxyurea scavenges free radicals and induces the expression of antioxidant genes in human cell cultures treated with hemin |
| author |
Santana, Sânzio Silva |
| author_facet |
Santana, Sânzio Silva Pitanga, Thassila Nogueira Santana, Jeanne Machado de Zanette, Dalila Lucíola Vieira, Jamile de Jesus Yahouédéhou, Sètondji Cocou Modeste Alexandre Adanho, Corynne Stephanie Ahouefa Viana, Sayonara de Melo Luz, Nivea Farias Borges, Valeria de Matos Goncalves, Marilda de Souza |
| author_role |
author |
| author2 |
Pitanga, Thassila Nogueira Santana, Jeanne Machado de Zanette, Dalila Lucíola Vieira, Jamile de Jesus Yahouédéhou, Sètondji Cocou Modeste Alexandre Adanho, Corynne Stephanie Ahouefa Viana, Sayonara de Melo Luz, Nivea Farias Borges, Valeria de Matos Goncalves, Marilda de Souza |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Santana, Sânzio Silva Pitanga, Thassila Nogueira Santana, Jeanne Machado de Zanette, Dalila Lucíola Vieira, Jamile de Jesus Yahouédéhou, Sètondji Cocou Modeste Alexandre Adanho, Corynne Stephanie Ahouefa Viana, Sayonara de Melo Luz, Nivea Farias Borges, Valeria de Matos Goncalves, Marilda de Souza |
| dc.subject.other.pt_BR.fl_str_mv |
Anemia falciforme Hidroxiureia Hemina Resposta antioxidante Nrf2 |
| topic |
Anemia falciforme Hidroxiureia Hemina Resposta antioxidante Nrf2 Sickle cell anemia Hydroxyurea Hemin Antioxidant response Nrf2 |
| dc.subject.en.en.fl_str_mv |
Sickle cell anemia Hydroxyurea Hemin Antioxidant response |
| dc.subject.en.pt_BR.fl_str_mv |
Nrf2 |
| description |
Brazilian National Council of Research (CNPq) (311888/2013-5) (MG) |
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2020 |
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2020-09-18T14:30:16Z |
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2020-09-18T14:30:16Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/43448 |
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1664-3224 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.3389/fimmu.2020.01488 |
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1664-3224 |
| identifier_str_mv |
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. 1664-3224 10.3389/fimmu.2020.01488 |
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Frontiers Media |
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Frontiers Media |
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