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:: Volume 9, Issue 1 (Int J Mol Cell Med [In press] 2020) ::
Int J Mol Cell Med 2020, 9(1): 0-0 Back to browse issues page
Angiotensin (1-7) Inhibits Ang II-mediated ERK1/2 Activation by Stimulating MKP-1 Activation in Vascular Smooth Muscle Cells
Alejandra Sousa-Lopes1, Raiany Alves de Freitas1, Fernando S. Carneiro2, Kenia P. Nunes3, Kyan J. Allahdadi4, R. Clinton Webb5, Rita C. Tostes2, Fernanda R. Giachini1, Victor Lima 6
1- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças, MT, Brazil.
2- Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
3- Department of Biomedical and Chemical Engineering and Sciences, Florida Institute of Technology, United States.
4- Biotechnology and Cell Therapy Center, São Rafael Hospital, Salvador, Brazil.
5- Department of Physiology, Augusta University, United States.
6- Institute of Biological and Health Sciences, Federal University of Mato Grosso, Barra do Garças, MT, Brazil. , vvlimaufmt@gmail.com
Abstract:   (205 Views)
The renin–angiotensin system (RAS) exerts profound physiological effects on blood pressure regulation and fluid homeostasis, mainly by modulating renal, cardiovascular, and central nervous systems. Angiotensin (Ang)-(1-7), an end-product of RAS, is recognized by its cardiovascular protective properties through stimulation of the Mas receptor, including vasodilation, anti-inflammatory, and antihypertensive actions, and consequently, counter-regulating the well-known Ang II-elicited actions. The overall hypothesis of this study is that Ang-(1-7) inhibits Ang II-induced ERK1/2 activation in vascular smooth muscle cells (VSMCs), via regulation of mitogen-activated protein phosphatase-1 (MKP-1) activity. Aortas from male Wistar rats were incubated with Ang-(1-7) or vehicle. Concentration-response curves to Ang II were performed in endothelium-denuded aortas, in the presence or absence of ERK1/2 (PD98059) inhibitor or Mas receptor (A-779) antagonist. Expression of proteins was assessed by western blot, and immunohistochemistry was conducted in VSMCs. Ang-(1-7) incubation decreased Ang II-induced contractile response in aortas, and this effect was not observed in the presence of PD98059 or A-779. Stimulation of VSMCs with Ang-(1-7) prevented Ang II-induced ERK1/2 phosphorylation, but not C-Raf-activation. Furthermore, Ang II decreased MKP-1 phosphorylation in VSMCs. Interestingly, simultaneous incubation of Ang-(1-7) with Ang II favored MKP-1 phosphorylation, negatively modulating ERK1/2 activation in VSMCs. The results suggest that Ang-(1-7) counter-regulates actions evoked by Ang II overproduction, as observed in cardiovascular diseases, mainly by modulating MKP-1 activity. This evidence suggests that the role of Ang-(1-7) in MKP-1-regulation represents a target for new therapeutic development.
Keywords: Angiotensin (1-7), ERK 1/2, MKP-1, angiotensin-II, renin-angiotensin system, VSMCs, MAPK phosphatase.
Full-Text [PDF 570 kb]   (15 Downloads)    
Type of Study: Original Article | Subject: Cell Biology
Received: 2020/03/25 | Accepted: 2020/06/13 | Published: 2020/04/29
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Sousa-Lopes A, Alves de Freitas R, S. Carneiro F, P. Nunes K, J. Allahdadi K, Webb R C, et al . Angiotensin (1-7) Inhibits Ang II-mediated ERK1/2 Activation by Stimulating MKP-1 Activation in Vascular Smooth Muscle Cells. Int J Mol Cell Med. 2020; 9 (1)
URL: http://ijmcmed.org/article-1-1282-en.html


Volume 9, Issue 1 (Int J Mol Cell Med [In press] 2020) Back to browse issues page
International Journal of Molecular and Cellular Medicine (IJMCM) International Journal of Molecular and Cellular Medicine (IJMCM)
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