Arginine decreases peroxisome proliferator-activated receptor-gamma activity via c-Jun

作者:Ban Kechen; Peng Zhanglong; Lin Wei; Kozar Rosemary A*
来源:Molecular and Cellular Biochemistry, 2012, 362(1-2): 7-13.
DOI:10.1007/s11010-011-1122-9

摘要

We have previously shown in the post ischemic gut that enteral arginine enhanced injury and inflammation via c-Jun/AP-1 and abrogated peroxisome proliferator-activated receptor (PPAR) gamma activity. In the current study, we investigated the mechanism by which arginine inhibited PPAR gamma in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPAR gamma transcriptional activity in a time and dose-dependent fashion. Furthermore, downregulation of PPAR gamma by arginine involved phosphorylation of c-Jun that occurred before to changes in PPAR gamma transcriptional activity. Silencing of c-Jun increased PPAR gamma beyond that of nonsilenced cells and was not mitigated by arginine. Using a series of blocking studies, we found no relationship between arginine and the ligand-dependent binding site of PPAR gamma. In conclusion, arginine decreased PPAR gamma transcriptional activity in small bowel intestinal epithelial cells. These changes are due, in part, to phosphorylation of c-Jun and may explain the deleterious effects of enteral arginine in the post ischemic gut.

  • 出版日期2012-3