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https://hdl.handle.net/2440/50752
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Type: | Journal article |
Title: | Blunted activation of NF-kappa B and NF-kappa B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response |
Author: | Hayakawa, K. Hiramatsu, N. Okamura, M. Yao, J. Paton, A. Paton, J. Kitamura, M. |
Citation: | Biochemical and Biophysical Research Communications, 2008; 365(1):47-53 |
Publisher: | Academic Press Inc |
Issue Date: | 2008 |
ISSN: | 0006-291X 1090-2104 |
Statement of Responsibility: | Kunihiro Hayakawa, Nobuhiko Hiramatsu, Maro Okamura, Jian Yao, Adrienne W. Paton, James C. Paton and Masanori Kitamura |
Abstract: | Geranylgeranylacetone (GGA), an anti-ulcer agent, has anti-inflammatory potential against experimental colitis and ischemia-induced renal inflammation. However, molecular mechanisms involved in its anti-inflammatory effects are largely unknown. We found that, in glomerular mesangial cells, GGA blocked activation of nuclear factor-κB and consequent induction of monocyte chemoattractant protein 1 (MCP-1) by inflammatory cytokines. It was inversely correlated with induction of unfolded protein response (UPR) evidenced by expression of 78 kDa glucose-regulated protein (GRP78) and suppression of endoplasmic reticulum stress-responsive alkaline phosphatase. Various inducers of UPR including tunicamycin, thapsigargin, A23187, 2-deoxyglucose, dithiothreitol, and AB5 subtilase cytotoxin reproduced the suppressive effects of GGA. Furthermore, attenuation of UPR by stable transfection with GRP78 diminished the anti-inflammatory effects of GGA. These results disclosed a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of GGA. |
Keywords: | Geranylgeranylacetone Mesangial cell Tumor necrosis factor-α Unfolded protein response Endoplasmic reticulum stress Monocyte chemoattractant protein 1 Nuclear factor-κB |
Description: | Copyright © 2008 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.bbrc.2007.10.115 |
Published version: | http://dx.doi.org/10.1016/j.bbrc.2007.10.115 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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