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Title: 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
Authors: Oliveira-Junior, Edgar Borges de
Thomazzi, Sara Maria
Relider, Jussara
Antunes, Edson
Condino-Neto, Antonio
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Sergipe
Universidade Estadual de Campinas (UNICAMP)
Universidade de São Paulo (USP)
Keywords: BAY 41-2272
human macrophage
myeloid cell
NADPH oxidase
Issue Date: 12-Jul-2007
Publisher: Elsevier B.V.
Citation: European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 567, n. 1-2, p. 43-49, 2007.
Abstract: We 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.
ISSN: 0014-2999
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