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Molecular and Cellular Biochemistry

, Volume 362, Issue 1–2, pp 7–13 | Cite as

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

  • Kechen Ban
  • Zhanglong Peng
  • Wei Lin
  • Rosemary A. Kozar
Article

Abstract

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.

Keywords

Arginine c-Jun Peroxisome proliferator-activated receptor-γ 

Abbreviations

AP-1

Activator protein 1

CBP

CREB binding protein

DMEM

Dulbecco’s modified Eagle’s medium

ERK

Extracellular signal-regulated protein kinase

FBS

Fetal bovine serum

iNOS

Inducible nitric oxide synthase

JNK

c-Jun NH2-terminal kinase

MAPK

Mitogen-activated protein kinases

PPAR

Peroxisome proliferator-activated receptor

PPRE

Peroxisome proliferator response elements

RXR

Retinoid X receptor

Notes

Acknowledgment

This study was supported by the National Institutes of Health RO1 GM077282.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Kechen Ban
    • 1
  • Zhanglong Peng
    • 1
  • Wei Lin
    • 1
  • Rosemary A. Kozar
    • 1
  1. 1.Department of SurgeryUniversity of Texas Health Science Center at HoustonHoustonUSA

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