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Angiotensin II activation of insulin-like growth factor 1 receptor transcription is mediated by a tyrosine kinase-dependent redox-sensitive mechanism.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Du, James Xianxing Peng, Tianqing Scheidegger, Kathrin J. Delafontaine, Patrick |
| Copyright Year | 1999 |
| Abstract | We have recently shown that angiotensin II activation of insulin-like growth factor 1 receptor (IGF-1R) transcription is a critical requirement for angiotensin-stimulated vascular smooth muscle cell growth; therefore, we examined the signaling pathway involved. In rat aortic smooth muscle cells, the antioxidants N-acetyl-L-cysteine (5 mmol/L) and pyrrolidine dithiocarbamate (100 micromol/L) completely inhibited angiotensin II-stimulated increases in IGF-1R mRNA and protein levels, suggesting the involvement of reactive oxygen species. Indeed, catalase abolished the Ang II-stimulated increase of IGF-1R protein expression, and accordingly, H(2)O(2) (0.2 mmol/L) or the oxidized products of linoleic acid, hydroperoxyoctadecadienoic acids (10 micromol/L), increased IGF-1R mRNA levels at 3 hours by 74+/-20% and 107+/-22% and increased receptor number at 24 hours by 51+/-6.7% and 55+/-7.4%, respectively. The protein tyrosine kinase inhibitors genistein and tyrphostin A25 also blocked angiotensin II increases in IGF-1R mRNA and protein levels and blocked the ability of hydroperoxyoctadecadienoic acids and H(2)O(2) to increase IGF-1R expression, suggesting that oxidative stress may be an early event in the angiotensin II signaling cascade. Furthermore, calcium chelation inhibited the angiotensin II effect. Transient transfection assays revealed that a (-2350)+640 IGF-1R promoter/luciferase construct was fully responsive to angiotensin II stimulation (127+/-20% increase). Ten millimoles per liter hydroperoxyoctadecadienoic acids and 0.2 mmol/L H(2)O(2) increased luciferase activity by 79+/-8.5% and 63+/-12%, respectively, and 5 mmol/L N-acetyl-L-cysteine blocked the angiotensin II-induced upregulation of luciferase activity by 70%. These data suggest that angiotensin II stimulates IGF-1R gene transcription via calcium-dependent activation of protein tyrosine kinase activity that lies downstream from an oxidant stimulus. These findings provide key insights into the signaling mechanisms whereby angiotensin II exerts its growth-promoting effects on the vasculature. |
| File Format | PDF HTM / HTML |
| DOI | 10.1161/01.ATV.19.9.2119 |
| PubMed reference number | 10479653 |
| Journal | Medline |
| Volume Number | 19 |
| Issue Number | 9 |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/atvbaha/19/9/2119.full.pdf?download=true |
| Alternate Webpage(s) | http://atvb.ahajournals.org/content/19/9/2119.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1161/01.ATV.19.9.2119 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
