PMID- 15345139
OWN - NLM
STAT- MEDLINE
DCOM- 20050816
LR  - 20231213
IS  - 1523-0864 (Print)
IS  - 1523-0864 (Linking)
VI  - 6
IP  - 5
DP  - 2004 Oct
TI  - Role of NF-kappaB and p38 MAP kinase signaling pathways in the 
      lipopolysaccharide-dependent activation of heme oxygenase-1 gene expression.
PG  - 802-10
AB  - 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 induction of HO-1 
      gene expression. The results suggest that the NF-kappaB and p38 MAPK signaling 
      pathways mediate the LPS-dependent induction of HO-1 gene expression via DNA 
      sequences of the proximal promoter region.
FAU - Wijayanti, Nastiti
AU  - Wijayanti N
AD  - Institut fur Klinische Chemie und Pathobiochemie, Justus-Liebig-Universitat 
      Giessen, D-35392 Giessen, Germany.
FAU - Huber, Sebastian
AU  - Huber S
FAU - Samoylenko, Anatoly
AU  - Samoylenko A
FAU - Kietzmann, Thomas
AU  - Kietzmann T
FAU - Immenschuh, Stephan
AU  - Immenschuh S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Enzyme Activation
MH  - *Enzyme Induction
MH  - Genes, Reporter
MH  - Heme Oxygenase (Decyclizing)/genetics/*metabolism
MH  - Heme Oxygenase-1
MH  - Lipopolysaccharides/*metabolism
MH  - *MAP Kinase Signaling System
MH  - Membrane Proteins
MH  - Mice
MH  - Monocytes/cytology/metabolism
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Rats
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
MH  - NF-kappaB-Inducing Kinase
EDAT- 2004/09/04 05:00
MHDA- 2005/08/17 09:00
CRDT- 2004/09/04 05:00
PHST- 2004/09/04 05:00 [pubmed]
PHST- 2005/08/17 09:00 [medline]
PHST- 2004/09/04 05:00 [entrez]
AID - 10.1089/ars.2004.6.802 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2004 Oct;6(5):802-10. doi: 10.1089/ars.2004.6.802.