Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients

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dc.citation.issue2
dc.citation.volume12
dc.contributor.authorNucci, Laura A. [UNIFESP]
dc.contributor.authorSantos, Sidneia S. [UNIFESP]
dc.contributor.authorBrunialti, Milena K. C. [UNIFESP]
dc.contributor.authorSharma, Narendra Kumar [UNIFESP]
dc.contributor.authorMachado, Flavia R. [UNIFESP]
dc.contributor.authorAssuncao, Murillo
dc.contributor.authorde Azevedo, Luciano C. P.
dc.contributor.authorSalomao, Reinaldo [UNIFESP]
dc.coverageSan Francisco
dc.date.accessioned2020-07-17T14:02:58Z
dc.date.available2020-07-17T14:02:58Z
dc.date.issued2017
dc.description.abstractBackground and objectives Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients. Materials and methods Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up-or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of <= 0.05 was considered significant. Results Twenty-two genes were differently expressed in D0 samplesen
dc.description.abstractmost of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signalingen
dc.description.abstractthe role of JAK1, JAK2 and TYK2 in interferon signalingen
dc.description.abstractmitochondrial dysfunctionen
dc.description.abstractand superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients. Conclusion Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients.en
dc.description.affiliationUniv Fed Sao Paulo, Hosp Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil
dc.description.affiliationHosp Israelita Albert Einstein, Sao Paulo, Brazil
dc.description.affiliationHosp Sirio Libanes, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Hosp Sao Paulo, Escola Paulista Med, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparoa Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientificoe Tecnologico (CNPq)
dc.description.sponsorshipIDFAPESP: 2011/20401-4
dc.description.sponsorshipIDCNPq: 305685/2011-2
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0172024
dc.identifier.citationPlos One. San Francisco, v. 12, n. 2, p. -, 2017.
dc.identifier.doi10.1371/journal.pone.0172024
dc.identifier.fileWOS000394231800142.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55110
dc.identifier.wosWOS:000394231800142
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleExpression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patientsen
dc.typeinfo:eu-repo/semantics/article
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