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Endothelin-1 Induced Phosphorylation of Caveolin-1 and Smad2C in Human Vascular Smooth Muscle Cells: Role of NADPH Oxidases, c-Abl, and Caveolae Integrity in TGF-β Receptor Transactivation
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Mahsa Hosseinipour1   , Mojtaba Rashidi1 , Faezeh Seif2 , Hossein Babaahmadi-Rezaei 3 |
1- Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
2- Department of Basic sciences, Shoushtar Faculty of Medical sciences, Shoushtar, Iran.
3- Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. , hbr.biomed@gmail.com |
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Abstract: (895 Views) |
| Caveolin-1(Cav-1) is one of the most important components of caveolae in the cell membrane, which plays an important role in cell signaling transduction, such as EGFR and TGF-β receptor transactivation. The purpose of this study was to evaluate the effect of c-Abl and NAD(P)H oxidases (NOX) on phosphorylation of Cav-1 and consequently their effect on phosphorylation of Smad2C induced by Endothelin-1 in human vascular smooth muscle cells (VSMCs). In this study, all experiments were performed using human VSMCs. The phosphorylation level of the Caveolin-1 and Smad2C proteins were assessed by western blotting using Phospho-Caveolin-1 (Tyr14) antibody and phospho-Smad2 (Ser465/467) antibody. The data were reported as mean ± SEM. The VSMCs treated with endothelin-1(ET-1) (100 nanomolar (nmol)) demonstrated a time-dependent increase in the pCav-1 level (p<0.05). The inhibitors of NOX (diphenyleneiodonium) (p<0.05), cholesterol depleting agent (beta-cyclodextrin) (p<0.05) and c-Abl inhibitor (PP1) (p<0.01) were able to reduce the level of the phospho-Cav-1 and phospho-Smad2C induced by Et-1 (p<0.05). Our results proposed that caveolae structure, NOX, c-Abl played an important role in the phosphorylation of Cav-1 induced by ET-1 in the human VSMCs. Furthermore, our findings showed that phosphoCav-1 involved in TGFR transactivation. Thus, Et-1 via a transactivation-dependent mechanism can cause phosphorylation of Smad2C. |
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| Keywords: Endothelin-1, Caveolin-1, c-Abl, NADPH oxidase, Smad2 protein |
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Full-Text [PDF 582 kb]
(597 Downloads)
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Type of Study: Original Article |
Subject:
Clinical Biochemistry
Received: 2022/11/6 | Accepted: 2023/07/26 | Published: 2023/07/26
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