Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/95855
Type: Artigo
Title: Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart
Author: Saad M.J.A.
Carvalho C.R.O.
Velloso L.A.
Abstract: We have investigated whether angiotensin II (AII) is able to induce insulin receptor substrate 1 (IRS-1) phosphorylation and its association with phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart in vivo. The phosphorylation state of IRS-1 following infusion of insulin or AII via the vena cava was assessed after immunoprecipitation with an anti-peptide antibody to IRS-1 followed by immunoblotting with an anti-phosphotyrosine antibody and an anti-PI 3-kinase antibody. Densitometry indicated a 5.6 ± 1.3-fold increase in IRS-1 phosphorylation after stimulation with AII and a 12.8 ± 3.1-fold increase after insulin. The effect was maximal at an AII concentration of 10-8 M and ocurred 1 min after infusion. There was also a 6.1 ± 1.2-fold increase in IRS-1-associated PI 3-kinase in response to AII. In the isolated perfused heart the result was similar, showing a direct effect of AII on this pathway. When the animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1 receptor) antagonist, there was a marked reduction in the AII-induced tyrosine phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated by the AT1 receptor. We conclude that AII stimulates tyrosine phosphorylation of IRS-1 and its association with PI 3-kinase. This pathway thus represents an additional signalling mechanism stimulated by AII in the rat heart in vivo.
We have investigated whether angiotensin II (AII) is able to induce insulin receptor substrate 1 (IRS-1) phosphorylation and its association with phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart in vivo. The phosphorylation state of IRS-1 following infusion of insulin or AII via the vena cava was assessed after immunoprecipitation with an anti-peptide antibody to IRS-1 followed by immunoblotting with an anti-phosphotyrosine antibody and an anti-PI 3-kinase antibody. Densitometry indicated a 5.6 +/- 1.3-fold increase in IRS-1 phosphorylation after stimulation with AII and a 12.8 +/- 3.1-fold increase after insulin. The effect was maximal at an AII concentration of 10(-8) M and occurred 1 min after infusion. There was also a 6.1 +/- 1.2-fold increase in IRS-1-associated PI 3-kinase in response to AII. In the isolated perfused heart the result was similar, showing a direct effect of AII on this pathway. When the animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1 receptor) antagonist, there was a marked reduction in the AII-induced tyrosine phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated by the AT1 receptor. We conclude that AII stimulates tyrosine phosphorylation of IRS-1 and its association with PI 3-kinase. This pathway thus represents an additional signalling mechanism stimulated by AII in the rat heart in vivo
Subject: Experimentação animal
Immunoblotting
Imunoprecipitação
Country: Inglaterra
Editor: Portland Press
Citation: Biochemical Journal. , v. 310, n. 3, p. 741 - 744, 1995.
Rights: fechado
Identifier DOI: 10.1042/BCJ20180457
Address: http://www.biochemj.org/content/310/3/741
Date Issue: 1995
Appears in Collections:FCM - Artigos e Outros Documentos

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