Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0069590 http://repositorio.unifesp.br/handle/11600/36549 |
Resumo: | Paracoccidioides brasiliensis, a causative agent of paracoccidioidomycosis (PCM), should be able to adapt to dramatic environmental changes inside the infected host after inhalation of air-borne conidia and transition to pathogenic yeasts. Proteins with antioxidant functions may protect fungal cells against reactive oxygen (ROS) and nitrogen (RNS) species generated by phagocytic cells, thus acting as potential virulence factors. Ras GTPases are involved in stress responses, cell morphology, and differentiation in a range of organisms. Ras, in its activated form, interacts with effector proteins and can initiate a kinase cascade. in lower eukaryotes, Byr2 kinase represents a Ras target. the present study investigated the role of Ras in P. brasiliensis after in vitro stimulus with ROS or RNS. We have demonstrated that low concentrations of H2O2 (0.1 mM) or NO2 (0.1-0.25 mu M) stimulated P. brasiliensis yeast cell proliferation and that was not observed when yeast cells were pre-incubated with farnesyltransferase inhibitor. We constructed an expression plasmid containing the Byr2 Ras-binding domain (RBD) fused with GST (RBD-Byr2-GST) to detect the Ras active form. After stimulation with low concentrations of H2O2 or NO2, the Ras active form was observed in fungal extracts. Besides, NO2 induced a rapid increase in S-nitrosylated Ras levels. This alternative posttranslational modification of Ras, probably in residue Cys123, would lead to an exchange of GDP for GTP and consequent GTPase activation in P. brasiliensis. in conclusion, low concentrations of H2O2 or NO2 stimulated P. brasiliensis proliferation through Ras activation. |
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Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent MannerParacoccidioides brasiliensis, a causative agent of paracoccidioidomycosis (PCM), should be able to adapt to dramatic environmental changes inside the infected host after inhalation of air-borne conidia and transition to pathogenic yeasts. Proteins with antioxidant functions may protect fungal cells against reactive oxygen (ROS) and nitrogen (RNS) species generated by phagocytic cells, thus acting as potential virulence factors. Ras GTPases are involved in stress responses, cell morphology, and differentiation in a range of organisms. Ras, in its activated form, interacts with effector proteins and can initiate a kinase cascade. in lower eukaryotes, Byr2 kinase represents a Ras target. the present study investigated the role of Ras in P. brasiliensis after in vitro stimulus with ROS or RNS. We have demonstrated that low concentrations of H2O2 (0.1 mM) or NO2 (0.1-0.25 mu M) stimulated P. brasiliensis yeast cell proliferation and that was not observed when yeast cells were pre-incubated with farnesyltransferase inhibitor. We constructed an expression plasmid containing the Byr2 Ras-binding domain (RBD) fused with GST (RBD-Byr2-GST) to detect the Ras active form. After stimulation with low concentrations of H2O2 or NO2, the Ras active form was observed in fungal extracts. Besides, NO2 induced a rapid increase in S-nitrosylated Ras levels. This alternative posttranslational modification of Ras, probably in residue Cys123, would lead to an exchange of GDP for GTP and consequent GTPase activation in P. brasiliensis. in conclusion, low concentrations of H2O2 or NO2 stimulated P. brasiliensis proliferation through Ras activation.Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Terapia Celular & Mol CTCMol, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenacao Aperfeicoamento de Pessoal de Nivel SuperiorFAPESP: 2011/14392-2CNPq: 477764/2009-6Public Library ScienceUniversidade Federal de São Paulo (UNIFESP)Haniu, Ana Eliza Coronel Janu [UNIFESP]Maricato, Juliana Terzi [UNIFESP]Mathias, Pedro Paulo Moraes [UNIFESP]Castilho, Daniele Goncalves [UNIFESP]Miguel, Rodrigo Bernardi [UNIFESP]Monteiro, Hugo Pequeno [UNIFESP]Puccia, Rosana [UNIFESP]Batista, Wagner Luiz [UNIFESP]2016-01-24T14:32:00Z2016-01-24T14:32:00Z2013-07-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11application/pdfhttp://dx.doi.org/10.1371/journal.pone.0069590Plos One. San Francisco: Public Library Science, v. 8, n. 7, 11 p., 2013.10.1371/journal.pone.0069590WOS000323369700051.pdf1932-6203http://repositorio.unifesp.br/handle/11600/36549WOS:000323369700051engPlos Oneinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-07-31T13:14:50Zoai:repositorio.unifesp.br/:11600/36549Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-07-31T13:14:50Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
title |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
spellingShingle |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner Haniu, Ana Eliza Coronel Janu [UNIFESP] |
title_short |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
title_full |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
title_fullStr |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
title_full_unstemmed |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
title_sort |
Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner |
author |
Haniu, Ana Eliza Coronel Janu [UNIFESP] |
author_facet |
Haniu, Ana Eliza Coronel Janu [UNIFESP] Maricato, Juliana Terzi [UNIFESP] Mathias, Pedro Paulo Moraes [UNIFESP] Castilho, Daniele Goncalves [UNIFESP] Miguel, Rodrigo Bernardi [UNIFESP] Monteiro, Hugo Pequeno [UNIFESP] Puccia, Rosana [UNIFESP] Batista, Wagner Luiz [UNIFESP] |
author_role |
author |
author2 |
Maricato, Juliana Terzi [UNIFESP] Mathias, Pedro Paulo Moraes [UNIFESP] Castilho, Daniele Goncalves [UNIFESP] Miguel, Rodrigo Bernardi [UNIFESP] Monteiro, Hugo Pequeno [UNIFESP] Puccia, Rosana [UNIFESP] Batista, Wagner Luiz [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Haniu, Ana Eliza Coronel Janu [UNIFESP] Maricato, Juliana Terzi [UNIFESP] Mathias, Pedro Paulo Moraes [UNIFESP] Castilho, Daniele Goncalves [UNIFESP] Miguel, Rodrigo Bernardi [UNIFESP] Monteiro, Hugo Pequeno [UNIFESP] Puccia, Rosana [UNIFESP] Batista, Wagner Luiz [UNIFESP] |
description |
Paracoccidioides brasiliensis, a causative agent of paracoccidioidomycosis (PCM), should be able to adapt to dramatic environmental changes inside the infected host after inhalation of air-borne conidia and transition to pathogenic yeasts. Proteins with antioxidant functions may protect fungal cells against reactive oxygen (ROS) and nitrogen (RNS) species generated by phagocytic cells, thus acting as potential virulence factors. Ras GTPases are involved in stress responses, cell morphology, and differentiation in a range of organisms. Ras, in its activated form, interacts with effector proteins and can initiate a kinase cascade. in lower eukaryotes, Byr2 kinase represents a Ras target. the present study investigated the role of Ras in P. brasiliensis after in vitro stimulus with ROS or RNS. We have demonstrated that low concentrations of H2O2 (0.1 mM) or NO2 (0.1-0.25 mu M) stimulated P. brasiliensis yeast cell proliferation and that was not observed when yeast cells were pre-incubated with farnesyltransferase inhibitor. We constructed an expression plasmid containing the Byr2 Ras-binding domain (RBD) fused with GST (RBD-Byr2-GST) to detect the Ras active form. After stimulation with low concentrations of H2O2 or NO2, the Ras active form was observed in fungal extracts. Besides, NO2 induced a rapid increase in S-nitrosylated Ras levels. This alternative posttranslational modification of Ras, probably in residue Cys123, would lead to an exchange of GDP for GTP and consequent GTPase activation in P. brasiliensis. in conclusion, low concentrations of H2O2 or NO2 stimulated P. brasiliensis proliferation through Ras activation. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-07-29 2016-01-24T14:32:00Z 2016-01-24T14:32:00Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0069590 Plos One. San Francisco: Public Library Science, v. 8, n. 7, 11 p., 2013. 10.1371/journal.pone.0069590 WOS000323369700051.pdf 1932-6203 http://repositorio.unifesp.br/handle/11600/36549 WOS:000323369700051 |
url |
http://dx.doi.org/10.1371/journal.pone.0069590 http://repositorio.unifesp.br/handle/11600/36549 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 8, n. 7, 11 p., 2013. 10.1371/journal.pone.0069590 WOS000323369700051.pdf 1932-6203 WOS:000323369700051 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
11 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1824718309907496960 |