Low Concentrations of Hydrogen Peroxide or Nitrite Induced of Paracoccidioides brasiliensis Cell Proliferation in a Ras-Dependent Manner

Detalhes bibliográficos
Autor(a) principal: Haniu, Ana Eliza Coronel Janu [UNIFESP]
Data de Publicação: 2013
Outros Autores: 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]
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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spelling 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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