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Id: lil-512762
Autor: Pan, Q; Yang, X. -H; Cheng, Y. -X.
Título: Angiotensin II stimulates MCP-1 production in rat glomerular endothelial cells via NAD(P)H oxidase-dependent nuclear factor-kappa B signaling
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;42(6):531-536, June 2009. ilus, graf.
Idioma: en.
Resumo: Angiotensin II (Ang II) plays a crucial role in the pathogenesis of renal diseases. The objective of the present study was to investigate the possible inflammatory effect of Ang II on glomerular endothelial cells and the underlying mechanism. We isolated and characterized primary cultures of rat glomerular endothelial cells (GECs) and observed that Ang II induced the synthesis of monocyte chemoattractant protein-1 (MCP-1) in GECs as demonstrated by Western blot. Ang II stimulation, at concentrations ranging from 0.1 to 10 µm, of rat GECs induced a rapid increase in the generation of reactive oxygen species as indicated by laser fluoroscopy. The level of p47phox protein, an NAD(P)H oxidase subunit, was also increased by Ang II treatment. These effects of Ang II on GECs were all reduced by diphenyleneiodonium (1.0 µm), an NAD(P)H oxidase inhibitor. Ang II stimulation also promoted the activation of nuclear factor-kappa B (NF-κB). Telmisartan (1.0 µm), an AT1 receptor blocker, blocked all the effects of Ang II on rat GECs. These data suggest that the inhibition of NAD(P)H oxidase-dependent NF-κB signaling reduces the increase in MCP-1 production by GECs induced by Ang II. This may provide a mechanistic basis for the benefits of selective AT1 blockade in dealing with chronic renal disease.
Descritores: Angiotensina II/farmacologia
/biossíntese
CHEMOKINE CCLTEMEFOS/biossíntese
Células Endoteliais/metabolismo
Glomérulos Renais/citologia
NADPH Oxidases/antagonistas & inibidores
NF-kappa B/metabolismo
-Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia
Western Blotting
Benzimidazóis/farmacologia
Benzoatos/farmacologia
/efeitos dos fármacos
CHEMOKINE CCLTEMEFOS/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Inflamação/metabolismo
Oniocompostos/farmacologia
Estresse Oxidativo/fisiologia
Ratos Sprague-Dawley
Espécies Reativas de Oxigênio/metabolismo
Limites: Animais
Ratos
Responsável: BR1.1 - BIREME



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