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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation

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Author(s):
Bruder-Nascimento, T. [1, 2, 3, 4] ; Chinnasamy, P. [3, 4] ; Riascos-Bernal, D. F. [3, 4, 5] ; Cau, S. B. [1] ; Callera, G. E. [2] ; Touyz, R. M. [2, 6] ; Tostes, R. C. [1] ; Sibinga, N. E. S. [3, 4]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Pharmacol, BR-05508 Sao Paulo - Brazil
[2] Univ Ottawa, Kidney Res Ctr, Ottawa, ON K1N 6N5 - Canada
[3] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Dept Med, Div Cardiovasc, Bronx, NY 10461 - USA
[4] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10461 - USA
[5] Pontificia Univ Javeriana, Fac Med, Dept Physiol Sci, Bogota - Colombia
[6] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark - Scotland
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY; v. 66, p. 18-26, JAN 2014.
Web of Science Citations: 33
Abstract

Fat1 is an atypical cadherin that controls vascular smooth muscle cell (VSMC) proliferation and migration. Nicotinamide adenine dinudeotide phosphate (NADPH) oxidase 1 (Nox1) is an important source of reactive oxygen species (ROS) in VSMCs. Angiotensin II (Mg II) induces the expression and/or activation of both Fat1 and Nox1 proteins. This study tested the hypothesis that Ang II-induced Fat1 activation and VSMC migration are mediated by Nox1-dependent ROS generation and redox signaling. Studies were performed in cultured VSMCs from Sprague-Dawley rats. Cells were treated with Ang II (1 prnol/L) for short (5 to 30 min) or long term stimulations (3 to 12 h) in the absence or presence of the antioxidant apocynin (10 mu mol/L), extracellular-signal-regulated kinases 1/2 ( Erk1/2) inhibitor P098059(1 mu mol/L), or Ang II type 1 receptor (AT1R) valsartan (1 mu mol/L). siRNA was used to knockdown Nox1 or Fat1. Cell migration was determined by Boyden chamber assay. Ang II increased Fat1 mRNA and protein levels and promoted Fat1 translocation to the cell membrane, responses that were inhibited by AT1R antagonist and antioxidant treatment. Downregulation of Nox1 inhibited the effects of Ang II on Fat1 protein expression. Nox1 protein induction, ROS generation, and p44/p42 MAPK phosphoiylation in response to Ang II were prevented by valsartan and apocynin, and Nox1 siRNA inhibited Ang II-induced ROS generation. Knockdown of Fat1 did not affect Ang II-mediated increases in Nox1 expression or ROS. Inhibition of p44/p42 MAPK phosphorylation by PD98059 abrogated the Ang II-induced increase in Fat1 expression and membrane translocation. Knockdown of Fat1 inhibited Ang Il-induced VSMC migration, which was also prevented by valsartan, apocynin, PD98059, and Nox1 siRNA. Our findings indicate that Ang II regulates Fat1 expression and activity and induces Fat1 -dependent VSMC migration via activation of AT1R, ERK1/2, and Nox1 -derived ROS, suggesting a role for Fat1 downstream of Ang II signaling that leads to vascular remodeling. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 11/01785-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular injury
Grantee:Thiago Bruder Do Nascimento
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 11/22035-5 - Contribution of oxidative stress and NADPH oxidase (NOXes) diabetes-associated vascular injury: study in knockout mice
Grantee:Thiago Bruder Do Nascimento
Support Opportunities: Scholarships abroad - Research Internship - Doctorate