Arginine decreases peroxisome proliferator-activated receptor-γ activity via c-Jun.
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) γ activity. In the current study, we investigated the mechanism by which arginine inhibited PPARγ in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPARγ transcriptional activity in a time and dose-dependent fashion. Furthermore, downregulation of PPARγ by arginine involved phosphorylation of c-Jun that occurred before to changes in PPARγ transcriptional activity. Silencing of c-Jun increased PPARγ 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 PPARγ. In conclusion, arginine decreased PPARγ 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.
Department of Surgery, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Kechen
K
Ban
Zhanglong
Z
Peng
Wei
W
Lin
Rosemary A
RA
Kozar
D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*
D047495:PPAR gamma; D034741:RNA, Small Interfering; D001120:Arginine; D048031:JNK Mitogen-Activated Protein Kinases