Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling

Detalhes bibliográficos
Autor(a) principal: Zhao, Yingxin
Data de Publicação: 2016
Outros Autores: Valbuena, Gustavo, Walker, David H., Gazi, Michal, Hidalgo, Marylin, De Sousa, Rita, Oteo, Jose Antonio, Goez, Yenny, Brasier, Allan R.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/4547
Resumo: Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762516/
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spelling Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin SignalingCadherinsCell MembraneCells, CulturedChromatography, LiquidCytokinesGolgi ApparatusHost-Pathogen InteractionsHuman Umbilical Vein Endothelial CellsHumansIntegrinsJanus KinasesLipopolysaccharidesMembrane ProteinsProteomeProteomicsRickettsia conoriiSTAT1 Transcription FactorSignal TransductionTandem Mass SpectrometryUbiquitinsInfecções Sistémicas e ZoonosesFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762516/Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re-emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. However, the integrated proteomic response of human endothelial cells to R. conorii infection is not known. In this study, we performed quantitative proteomic profiling of primary human umbilical vein endothelial cells (HUVECs) with established R conorii infection versus those stimulated with endotoxin (LPS) alone. We observed differential expression of 55 proteins in HUVEC whole cell lysates. Of these, we observed induction of signal transducer and activator of transcription (STAT)1, MX dynamin-like GTPase (MX1), and ISG15 ubiquitin-like modifier, indicating activation of the JAK-STAT signaling pathway occurs in R. conorii-infected HUVECs. The down-regulated proteins included those involved in the pyrimidine and arginine biosynthetic pathways. A highly specific biotinylated cross-linking enrichment protocol was performed to identify dysregulation of 11 integral plasma membrane proteins that included up-regulated expression of a sodium/potassium transporter and down-regulation of α-actin 1. Analysis of Golgi and soluble Golgi fractions identified up-regulated proteins involved in platelet-endothelial adhesion, phospholipase activity, and IFN activity. Thirty four rickettsial proteins were identified with high confidence in the Golgi, plasma membrane, or secreted protein fractions. The host proteins associated with rickettsial infections indicate activation of interferon-STAT signaling pathways; the disruption of cellular adhesion and alteration of antigen presentation pathways in response to rickettsial infections are distinct from those produced by nonspecific LPS stimulation. These patterns of differentially expressed proteins suggest mechanisms of pathogenesis as well as methods for diagnosis and monitoring Rickettsia infections.This work was supported by NIAID Clinical Proteomics Center Grant HHSN272200800048C (to A.R.B.), University of Texas Medical Branch Clinical and Translational Science Award (CTSA) UL1TR000071 (to A.R.B.), and NIEHS Grant P30 ES006676 (to A.R.B.).American Society for Biochemistry and Molecular BiologyRepositório Científico do Instituto Nacional de SaúdeZhao, YingxinValbuena, GustavoWalker, David H.Gazi, MichalHidalgo, MarylinDe Sousa, RitaOteo, Jose AntonioGoez, YennyBrasier, Allan R.2017-03-07T15:46:25Z2016-012016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/4547engMol Cell Proteomics. 2016 Jan;15(1):289-304. doi: 10.1074/mcp.M115.054361. Epub 2015 Nov 111535-947610.1074/mcp.M115.054361info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:40:23Zoai:repositorio.insa.pt:10400.18/4547Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:39:19.769221Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
title Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
spellingShingle Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
Zhao, Yingxin
Cadherins
Cell Membrane
Cells, Cultured
Chromatography, Liquid
Cytokines
Golgi Apparatus
Host-Pathogen Interactions
Human Umbilical Vein Endothelial Cells
Humans
Integrins
Janus Kinases
Lipopolysaccharides
Membrane Proteins
Proteome
Proteomics
Rickettsia conorii
STAT1 Transcription Factor
Signal Transduction
Tandem Mass Spectrometry
Ubiquitins
Infecções Sistémicas e Zoonoses
title_short Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
title_full Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
title_fullStr Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
title_full_unstemmed Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
title_sort Endothelial Cell Proteomic Response to Rickettsia conorii Infection Reveals Activation of the Janus Kinase (JAK)-Signal Transducer and Activator of Transcription (STAT)-Inferferon Stimulated Gene (ISG)15 Pathway and Reprogramming Plasma Membrane Integrin/Cadherin Signaling
author Zhao, Yingxin
author_facet Zhao, Yingxin
Valbuena, Gustavo
Walker, David H.
Gazi, Michal
Hidalgo, Marylin
De Sousa, Rita
Oteo, Jose Antonio
Goez, Yenny
Brasier, Allan R.
author_role author
author2 Valbuena, Gustavo
Walker, David H.
Gazi, Michal
Hidalgo, Marylin
De Sousa, Rita
Oteo, Jose Antonio
Goez, Yenny
Brasier, Allan R.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Zhao, Yingxin
Valbuena, Gustavo
Walker, David H.
Gazi, Michal
Hidalgo, Marylin
De Sousa, Rita
Oteo, Jose Antonio
Goez, Yenny
Brasier, Allan R.
dc.subject.por.fl_str_mv Cadherins
Cell Membrane
Cells, Cultured
Chromatography, Liquid
Cytokines
Golgi Apparatus
Host-Pathogen Interactions
Human Umbilical Vein Endothelial Cells
Humans
Integrins
Janus Kinases
Lipopolysaccharides
Membrane Proteins
Proteome
Proteomics
Rickettsia conorii
STAT1 Transcription Factor
Signal Transduction
Tandem Mass Spectrometry
Ubiquitins
Infecções Sistémicas e Zoonoses
topic Cadherins
Cell Membrane
Cells, Cultured
Chromatography, Liquid
Cytokines
Golgi Apparatus
Host-Pathogen Interactions
Human Umbilical Vein Endothelial Cells
Humans
Integrins
Janus Kinases
Lipopolysaccharides
Membrane Proteins
Proteome
Proteomics
Rickettsia conorii
STAT1 Transcription Factor
Signal Transduction
Tandem Mass Spectrometry
Ubiquitins
Infecções Sistémicas e Zoonoses
description Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762516/
publishDate 2016
dc.date.none.fl_str_mv 2016-01
2016-01-01T00:00:00Z
2017-03-07T15:46:25Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/4547
url http://hdl.handle.net/10400.18/4547
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Mol Cell Proteomics. 2016 Jan;15(1):289-304. doi: 10.1074/mcp.M115.054361. Epub 2015 Nov 11
1535-9476
10.1074/mcp.M115.054361
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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