| First Author | Urata Y | Year | 1996 |
| Journal | J Biol Chem | Volume | 271 |
| Issue | 25 | Pages | 15146-52 |
| PubMed ID | 8662965 | Mgi Jnum | J:33700 |
| Mgi Id | MGI:81177 | Doi | 10.1074/jbc.271.25.15146 |
| Citation | Urata Y, et al. (1996) Long exposure to high glucose concentration impairs the responsive expression of gamma-glutamylcysteine synthetase by interleukin-1beta and tumor necrosis factor-alpha in mouse endothelial cells. J Biol Chem 271(25):15146-52 |
| abstractText | To elucidate the pathological metabolism of glutathione synthesis in diabetic endothelial cells, we studied the expression of gamma-glutamylcysteine synthetase (gamma-GCS) using a mouse vascular endothelial cell line. Exposing normoglycemic endothelial cells to tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta) increased the activity and the mRNA expression of gamma-GCS. The addition of inhibitors for nuclear factor kappaB (NF-kappaB) to the cells caused a loss of the gamma-GCS mRNA expression in response to TNF-alpha. A shift of the concentration of glucose in the medium from 5.5 to 28 mM glucose and a following incubation for 7 days decreased the expression of gamma-GCS mRNA. These cells showed no apparent responses of gamma-GCS mRNA or the activity of NF-kappaB to TNF-alpha or IL-beta. Increase in the GSH concentration of the cells treated with 28 mM glucose restored the expression of gamma-GCS mRNA and its response to TNF-alpha or IL-beta, suggesting that redox regulation is involved in the expression of gamma-GCS. In summary, the expression of gamma-GCS is regulated by TNF-alpha or IL-1beta in endothelial cells mediated by NF-kappaB stimulation, and impairment of the regulation of gamma-GCS in hyperglycemic cells may be a cause of medical complications that develop in diabetes mellitus. |
