Effects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cells

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dc.contributor.authorOliveira-Junior, Edgar Borges de
dc.contributor.authorThomazzi, Sara Maria
dc.contributor.authorRelider, Jussara
dc.contributor.authorAntunes, Edson
dc.contributor.authorCondino-Neto, Antonio
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Sergipe
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T13:48:52Z
dc.date.available2016-01-24T13:48:52Z
dc.date.issued2007-07-12
dc.description.abstractWe investigated the effects of the 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272) on the NADPH oxidase activity, gp91(phox) gene expression, cyclic guanosine-3',5-monophosphate (cGMP) and cyclic adenosine-3',5'-monophosphate (cAMP) levels in the human myelomonocytic THP-1 cell line. THP-1 cells treated with BAY 41-2272 (0.3-10 mu M) for 48 h significantly increased the superoxide anion (O-2(center dot-)) release. This increase was not affected when cells were pre-treated with the specific cGMP-phosphodiesterase inhibitor zaprinast, the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (ODQ), the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl) adenine (SQ 22,536) or the nitric oxide synthase inhibitor N-omega-nitro-1-arginine methyl ester (I-NAME). in addition, BAY 41-2272 (3 and 10 mu M; 48 h) was able to increase gp91(phox) gene expression on THP-1 cells. the pre-treatment with zaprinast, 3-isobutyl-L-methyl-xanthine (IBMX; 0.5 mM), ODQ, SQ 22,536 or l-NAME caused no additional effect on the expression of gp91(phox) evoked by BAY 41-2272. Treatment of THP-1 cells with BAY 41-2272 caused a significant increase in cGMP and cAMP levels. Our findings show that BAY 41-2272 caused a significant increase on the O-2(center dot-) release and gp91(phox) gene expression by THP-1 cells, and an elevation of intracellular cGMP and cAMP levels. However, we could not detect a clear correlation between both O-2(center dot-) release and gp91(phox) gene expression with activation of cGMP and cAMP signaling pathways. (c) 2007 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Estadual Campinas, Sch Med, Fac Med Sci, Dept Pediat, Campinas, SP, Brazil
dc.description.affiliationUniv Fed Sergipe, Dept Physiol, Aracaju, Brazil
dc.description.affiliationUniv Estadual Campinas, Sch Med, Fac Med Sci, Dept Pharmacol, Campinas, SP, Brazil
dc.description.affiliationUniv São Paulo, Inst Biomed Sci, Dept Immunol, São Paulo, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent43-49
dc.identifierhttp://dx.doi.org/10.1016/j.ejphar.2007.04.018
dc.identifier.citationEuropean Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 567, n. 1-2, p. 43-49, 2007.
dc.identifier.doi10.1016/j.ejphar.2007.04.018
dc.identifier.issn0014-2999
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/29876
dc.identifier.wosWOS:000247281700006
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofEuropean Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectBAY 41-2272en
dc.subjectcAMPen
dc.subjectcGMPen
dc.subjectgp91(phox)en
dc.subjecthuman macrophageen
dc.subjectmyeloid cellen
dc.subjectNADPH oxidaseen
dc.subjectphagocyteen
dc.titleEffects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cellsen
dc.typeinfo:eu-repo/semantics/article
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