Role of NF-kappaB and p38 MAP kinase signaling pathways in the lipopolysaccharide-dependent activation of heme oxygenase-1 gene expression

Antioxidants & Redox Signaling
Nastiti WijayantiS Immenschuh

Abstract

Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation, which is up-regulated by a host of stress stimuli. The bacterial cell membrane component lipopolysaccharide (LPS) is a prototypical activator of monocytic cells. Here, it is shown that LPS induced the endogenous HO-1 gene expression in RAW264.7 monocytic cells. To investigate the molecular mechanisms of HO-1 gene induction by LPS, we performed transfection experiments with reporter gene constructs containing sequences of the proximal rat HO-1 gene promoter. Deletion and mutation analysis indicated that a cyclic AMP response element/activator protein-1 site (-664/-657), but not an E-box motif (-47/-42), played a major role for LPS-dependent HO-1 gene induction. Up-regulation of HO-1 promoter activity by LPS was decreased by pharmacological nuclear factor-kappaB (NF-kappaB) inhibitors and by cotransfected expression vectors with dominant negative isoforms of NF-kappaB-inducing kinase, inhibitor of NF-kappaB (IkappaB) kinase beta, and IkappaBalpha. Moreover, the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and overexpressed dominant negative p38beta decreased, whereas dominant negative p38delta increased, LPS-dependent...Continue Reading

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Citations

Sep 4, 2004·Antioxidants & Redox Signaling·Mahin D Maines
Dec 17, 2005·Antioxidants & Redox Signaling·Auemduan PrawanYoung-Joon Surh
Dec 17, 2005·Antioxidants & Redox Signaling·Mahin D Maines
Feb 4, 2009·Antioxidants & Redox Signaling·Jeremy L HerrmannDaniel R Meldrum
Oct 3, 2008·Neuropsychiatric Disease and Treatment·Shigeru MaedaTakuya Miyawaki
Jul 2, 2010·World Journal of Gastroenterology : WJG·Vijith VijayanStephan Immenschuh
Nov 28, 2014·Cellular and Molecular Life Sciences : CMLS·Marisol ChangAida Habtezion
Aug 25, 2016·Scientific Reports·Chin-Kai TsengJin-Ching Lee
Oct 4, 2017·Antioxidants & Redox Signaling·Yao-Yu GongYu Huang
May 12, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tihomir MiralemMahin D Maines
Feb 20, 2015·Thrombosis and Haemostasis·Nina KozlovaThomas Kietzmann

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