| First Author | Chang JS | Year | 2008 |
| Journal | Circ Res | Volume | 102 |
| Issue | 8 | Pages | 905-13 |
| PubMed ID | 18323529 | Mgi Jnum | J:149031 |
| Mgi Id | MGI:3847400 | Doi | 10.1161/CIRCRESAHA.107.165308 |
| Citation | Chang JS, et al. (2008) Oxygen deprivation triggers upregulation of early growth response-1 by the receptor for advanced glycation end products. Circ Res 102(8):905-13 |
| abstractText | Myocardial infarction, stroke, and venous thromboembolism are characterized by oxygen deprivation. In hypoxia, biological responses are activated that evoke tissue damage. Rapid activation of early growth response-1 in hypoxia upregulates fundamental inflammatory and prothrombotic stress genes. We probed the mechanisms mediating regulation of early growth response-1 and demonstrate that hypoxia stimulates brisk generation of advanced glycation end products (AGEs) by endothelial cells. Via AGE interaction with their chief signaling receptor, RAGE, membrane translocation of protein kinase C-betaII occurs, provoking phosphorylation of c-Jun NH(2)-terminal kinase and increased transcription of early growth response-1 and its downstream target genes. These findings identify RAGE as a master regulator of tissue stress elicited by hypoxia and highlight this receptor as a central therapeutic target to suppress the tissue injury-provoking effects of oxygen deprivation. |
