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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
pharmacology, toxicology and pharmaceutics
Angiotensin-(1-7) inhibits epidermal growth factor receptor transactivation via a Mas receptor-dependent pathway
British Journal of Pharmacology, Volume 165, No. 5, Year 2012
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Description
BACKGROUND AND PURPOSE The transactivation of the epidermal growth factor (EGF) receptor appears to be an important central transduction mechanism in mediating diabetes-induced vascular dysfunction. Angiotensin-(1-7) [Ang-(1-7)] via its Mas receptor can prevent the development of hyperglycaemia-induced cardiovascular complications. Here, we investigated whether Ang-(1-7) can inhibit hyperglycaemia-induced EGF receptor transactivation and its classical signalling via ERK1/2 and p38 MAPK in vivo and in vitro. EXPERIMENTAL APPROACH Streptozotocin-induced diabetic rats were chronically treated with Ang-(1-7) or AG1478, a selective EGF receptor inhibitor, for 4 weeks and mechanistic studies performed in the isolated mesenteric vasculature bed as well as in primary cultures of vascular smooth muscle cells (VSMCs). KEY RESULTS Diabetes significantly enhanced phosphorylation of EGF receptor at tyrosine residues Y992, Y1068, Y1086, Y1148, as well as ERK1/2 and p38 MAPK in the mesenteric vasculature bed whereas these changes were significantly attenuated upon Ang-(1-7) or AG1478 treatment. In VSMCs grown in conditions of high glucose (25 mM), an Src-dependent elevation in EGF receptor phosphorylation was observed. Ang-(1-7) inhibited both Ang II- and glucose-induced transactivation of EGF receptor. The inhibition of high glucose-mediated Src-dependant transactivation of EGF receptor by Ang-(1-7) could be prevented by a selective Mas receptor antagonist, D-Pro7-Ang-(1-7). CONCLUSIONS AND IMPLICATIONS These results show for the first time that Ang-(1-7) inhibits EGF receptor transactivation via a Mas receptor/Src-dependent pathway and might represent a novel general mechanism by which Ang-(1-7) exerts its beneficial effects in many disease states including diabetes-induced vascular dysfunction. © 2011 The Authors. British Journal of Pharmacology.
Authors & Co-Authors
Akhtar, Saghir
Kuwait, Kuwait City
Kuwait University
Yousif, Mariam H.M.
Kuwait, Kuwait City
Kuwait University
Dhaunsi, Gursev Singh
Kuwait, Kuwait City
Kuwait University
Chandrasekhar, Bindu
Kuwait, Kuwait City
Kuwait University
Al-Farsi, Omama
Kuwait, Kuwait City
Kuwait University
Benter, Ibrahim Fadil
Kuwait, Kuwait City
Kuwait University
Statistics
Citations: 55
Authors: 6
Affiliations: 1
Identifiers
Doi:
10.1111/j.1476-5381.2011.01613.x
ISSN:
00071188
e-ISSN:
14765381
Research Areas
Noncommunicable Diseases