GW24-e2208 Dopamine D1-like receptors suppress proliferation of vascular smooth muscle cell induced by insulin-like growth factor-1
| Autor: | Chunyu Zeng, Duofen He, Shuo Zheng, Di Yang, Kou Xun, Yu Han, Lin Zhou, Jinjuan Fu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Fenoldopam business.industry Receptor expression medicine.medical_treatment Cell biology Insulin-like growth factor Endocrinology Dopamine receptor Internal medicine Medicine Cardiology and Cardiovascular Medicine business Receptor Protein kinase B PI3K/AKT/mTOR pathway medicine.drug |
| Zdroj: | Heart. 99:A62.1-A62 |
| ISSN: | 1468-201X 1355-6037 |
| DOI: | 10.1136/heartjnl-2013-304613.171 |
| Popis: | Objectives Proliferation of vascular smooth muscle cells (VSMCs) participates in the pathogenesis and development of cardiovascular diseases, including essential hypertension and atherosclerosis. Our previous study found that stimulation of D 1 -like dopamine receptors inhibited insulin-induced proliferation of VSMCs. Insulin-like growth factor-1 (IGF-1) and insulin share similar structure and biological effect. However, whether or not there is any effect of D 1 -like receptors on IGF-1-induced proliferation of VSMCs is not known. Therefore, we investigated the inhibitory effect of D 1 -like dopamine receptors on the IGF-1-induced VSMCs proliferation in this study. Methods VSMC proliferation was determined by [ 3 H]-thymidinein corporation, the uptake of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell number. Phosphorylated/non-phosphorylated IGF-1 receptor, Akt, mTOR and p70S6K expressions were determined by immunoblotting. The oligodeoxynucleotides were transfected to A10 cells to identify the effect of D 1 and D 5 receptors respectively. Results IGF-1 increased the proliferation of VSMCs, while in the presence of fenoldopam, IGF-1 mediated stimulatory effect was reduced. Use of either the antisense for D 1 or D 5 receptor partially inhibited the fenoldopam-induced anti-proliferation effect of VSMCs. Use of both D 1 andD 5 receptor antisenses completely blocked the inhibitory effect of fenoldopam. In the presence of PI3k and mTOR inhibitors, the IGF-1 mediated proliferation of VSMCs was blocked. Moreover, IGF-1 increased the phosphorylation of PI3k and mTOR. The inhibitory effect of fenoldopam on VSMC proliferation might be due to the inhibition of IGF-1 receptor expression and IGF-1 phosphorylation, since in the presence offenoldopam, the stimulatory effect of IGF-1 on phosphorylation of IGF-1 receptor, PI3k and mTOR is reduced, the IGF-1 receptor expression was reducedin A10 cells. Conclusions Activation of the D 1 -like receptors suppressed the proliferative effect of IGF-1 in A10 cells via the inhibition of the IGF-1R/Akt/mTOR/p70S6K pathway. |
| Databáze: | OpenAIRE |
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