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|Title:||Blunted activation of NF-kappa B and NF-kappa B-dependent gene expression by geranylgeranylacetone: Involvement of unfolded protein response|
|Citation:||Biochemical and Biophysical Research Communications, 2008; 365(1):47-53|
|Publisher:||Academic Press Inc|
|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.|
|Appears in Collections:||Molecular and Biomedical Science publications|
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