Hypusine modification of the ribosome-binding protein eIF5A, a target for new anti-inflammatory drugs: Understanding the action of the inhibitor GC7 on a murine macrophage cell line

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dc.contributor.authorde Almeida Jr., Oedem Paulo [UNESP]
dc.contributor.authorToledo, Thais Regina [UNESP]
dc.contributor.authorRossi, Danuza [UNESP]
dc.contributor.authorRossetto, Daniella de Barros [UNESP]
dc.contributor.authorWatanabe, Tatiana Faria [UNESP]
dc.contributor.authorGalvão, Fábio Carrilho [UNESP]
dc.contributor.authorMedeiros, Alexandra Ivo [UNESP]
dc.contributor.authorZanelli, Cleslei Fernando [UNESP]
dc.contributor.authorValentini, Sandro Roberto [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2018-12-11T16:55:28Z
dc.date.available2018-12-11T16:55:28Z
dc.date.issued2014-01-30
dc.description.abstractInflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component lipopolysaccharide (LPS), which induces the activation of innate immune response cells, the release of proinflammatory cytokines, such as interleukin 1 and tumor necrosis factor α (TNF-α), and the cellular generation of nitric oxide (NO) by the inducible nitric oxide synthase (iNOS). Although essential to the immune response, uncontrolled inflammatory responses can lead to pathological conditions, such as sepsis and rheumatoid arthritis. Therefore, identifying cellular targets for new anti-inflammatory treatments is crucial to improving therapeutic control of inflammation-related diseases. More recently, the translation factor eIF5A has been demonstrated to have a proinflammatory role in the release of cytokines and the production of NO. As eIF5A requires and essential and unique modification of a specific residue of lysine, changing it to hypusine, eIF5A is an interesting cellular target for anti-inflammatory treatment. The present study reviews the literature concerning the anti-inflammatory effects of inhibiting eIF5A function. We also present new data showing that the inhibition of eIF5A function by the small molecule GC7 significantly decreases TNF-α release without affecting TNF-α mRNA levels. We discuss the mechanisms by which eIF5A may interfere with TNF-α mRNA translation by binding to and regulating the function of ribosomes during protein synthesis. © 2014 Bentham Science Publishers.en
dc.description.affiliationDepartment of Biological Sciences School of Pharmaceutical Sciences Univ Estadual Paulista - UNESP, Araraquara-SP
dc.description.affiliationUnespDepartment of Biological Sciences School of Pharmaceutical Sciences Univ Estadual Paulista - UNESP, Araraquara-SP
dc.format.extent284-292
dc.identifierhttp://dx.doi.org/10.2174/13816128113199990036
dc.identifier.citationCurrent Pharmaceutical Design, v. 20, n. 2, p. 284-292, 2014.
dc.identifier.doi10.2174/13816128113199990036
dc.identifier.issn1381-6128
dc.identifier.issn1873-4286
dc.identifier.lattes1525665408900195
dc.identifier.orcid0000-0001-7831-1149
dc.identifier.scopus2-s2.0-84892960491
dc.identifier.urihttp://hdl.handle.net/11449/171475
dc.language.isoeng
dc.relation.ispartofCurrent Pharmaceutical Design
dc.relation.ispartofsjr0,883
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectAnti-inflammatory drugs
dc.subjectCG7
dc.subjectEIF5A
dc.subjectHypusine modification inhibitor
dc.subjectTNF-α
dc.titleHypusine modification of the ribosome-binding protein eIF5A, a target for new anti-inflammatory drugs: Understanding the action of the inhibitor GC7 on a murine macrophage cell lineen
dc.typeResenha
unesp.author.lattes8756770929017974[7]
unesp.author.lattes1525665408900195[8]
unesp.author.orcid0000-0001-6048-3647[7]
unesp.author.orcid0000-0001-7831-1149[8]

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