PMID- 11356853
OWN - NLM
STAT- MEDLINE
DCOM- 20010823
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 29
DP  - 2001 Jul 20
TI  - Cobalt induces heme oxygenase-1 expression by a hypoxia-inducible 
      factor-independent mechanism in Chinese hamster ovary cells: regulation by Nrf2 
      and MafG transcription factors.
PG  - 27018-25
AB  - We have shown previously that activation of the heme oxygenase-1 (ho-1) gene by 
      hypoxia in aortic smooth muscle cells is mediated by hypoxia-inducible factor-1 
      (HIF-1). In mutant (Ka13) Chinese hamster ovary cells lacking HIF activity, 
      accumulation of ho-1 mRNA in response to hypoxia and the hypoxia-mimetic CoCl(2) 
      was similar to that observed in wild type (K1) cells. These results support the 
      existence of HIF-dependent and HIF-independent mechanisms for ho-1 gene 
      activation by hypoxia and CoCl(2). In Ka13 cells, CoCl(2) stimulated expression 
      of a luciferase reporter gene under the control of a 15-kilobase pair mouse ho-1 
      promoter (pHO15luc). Mutation analyses identified the cobalt-responsive sequences 
      as the stress-response elements (StREs). In electrophoretic mobility shift 
      assays, two specific StRE-protein complexes were observed using extracts from 
      Ka13 cells. In response to cobalt, the level of the slower migrating complex X 
      increased, whereas that of complex Y decreased, in a time-dependent manner. 
      Members of the AP-1 superfamily of basic-leucine zipper factors bind to the StRE. 
      Antibody supershift electrophoretic mobility shift assays did not detect Jun, 
      Fos, or ATF/CREB proteins but identified Nrf2 and the small Maf protein, MafG, as 
      components of complex X. Furthermore, dominant-negative mutants of Nrf2 and small 
      Maf, but not of other bZIP factors, attenuated cobalt-mediated gene activation. 
      Additional experiments demonstrated that induction by cobalt does not result from 
      increased expression of MafG or regulated nuclear translocation of Nrf2 but is 
      dependent on cellular oxidative stress. Unlike cobalt, hypoxia did not stimulate 
      pHO15luc expression and did not increase StRE binding activity, indicating 
      distinct mechanisms for ho-1 gene activation by cobalt and hypoxia in Chinese 
      hamster ovary cells.
FAU - Gong, P
AU  - Gong P
AD  - Department of Molecular Genetics, Alton Ochsner Medical Foundation, New Orleans, 
      Louisiana 70121, USA.
FAU - Hu, B
AU  - Hu B
FAU - Stewart, D
AU  - Stewart D
FAU - Ellerbe, M
AU  - Ellerbe M
FAU - Figueroa, Y G
AU  - Figueroa YG
FAU - Blank, V
AU  - Blank V
FAU - Beckman, B S
AU  - Beckman BS
FAU - Alam, J
AU  - Alam J
LA  - eng
GR  - DK-43135/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010516
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MafG Transcription Factor)
RN  - 0 (Mafg protein, mouse)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Repressor Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 3G0H8C9362 (Cobalt)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Cobalt/*pharmacology
MH  - Cricetinae
MH  - Cricetulus
MH  - DNA Primers
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Gene Expression Regulation, Enzymologic/*drug effects/physiology
MH  - Heme Oxygenase (Decyclizing)/*genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - MafG Transcription Factor
MH  - Mutation
MH  - NF-E2-Related Factor 2
MH  - Nuclear Proteins/*physiology
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - Repressor Proteins/genetics/*physiology
MH  - Trans-Activators/genetics/*physiology
MH  - *Transcription Factors
MH  - Transcriptional Activation
EDAT- 2001/05/18 10:00
MHDA- 2001/08/24 10:01
CRDT- 2001/05/18 10:00
PHST- 2001/05/18 10:00 [pubmed]
PHST- 2001/08/24 10:01 [medline]
PHST- 2001/05/18 10:00 [entrez]
AID - S0021-9258(20)89818-4 [pii]
AID - 10.1074/jbc.M103658200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Jul 20;276(29):27018-25. doi: 10.1074/jbc.M103658200. Epub 2001 
      May 16.