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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
Statement of
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
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Appears in Collections:Aurora harvest 5
Molecular and Biomedical Science publications

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