Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis

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Sharifat, Narges
Zadeh, Ghorban Mohammad
Ghaffari, Mohammad-Ali
Dayati, Parisa
Kamato, Danielle
Little, Peter J
Babaahmadi-Rezaei, Hossein
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2017
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Abstract

Objective: G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TβRI in bovine aortic endothelial cells (BAECs). Method: The in-vitro model used BAECs. Signalling intermediate phospho-Smad2 in the carboxy terminal was detected and quantified by Western blotting. Key finding: ET-1 treatment of BAECs resulted in a time and concentration-dependent increase in pSmad2C. Peak phosphorylation was evident with 100 nm treatment of ET-1 at 4–6 h. TβRI antagonist, SB431542 inhibited ET-1-mediated pSmad2C. In the presence of bosentan, a mixed ETA and ETB receptor antagonist ET-1-mediated pSmad2C levels were inhibited. The ET-mediated pSmad2C was blocked by the protein synthesis inhibitor, cycloheximide. Conclusion: In BAECs, ET-1 via the ETB receptor is involved in transactivation of the TβRI. The transactivation-dependent response is dependent upon de novo protein synthesis.

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Journal of Pharmacy and Pharmacology
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69
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1
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© 2017 Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Pharmacy and Pharmacology following peer review. The definitive publisher-authenticated version Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis, Journal of Pharmacy and Pharmacology, 69 (1), pp. 66-72, 2017 is available online at: http://doi.org/10.1111/jphp.12654.
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Pharmacology and pharmaceutical sciences
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
atherosclerosis
endothelin-1
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Sharifat, N; Zadeh, GM; Ghaffari, M-A; Dayati, P; Kamato, D; Little, PJ; Babaahmadi-Rezaei, H, Endothelin-1 (ET-1) stimulates carboxy terminal Smad2 phosphorylation in vascular endothelial cells by a mechanism dependent on ET receptors and de novo protein synthesis, Journal of Pharmacy and Pharmacology, 2017, 69 (1), pp. 66-72
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