PMID- 10751553
OWN - NLM
STAT- MEDLINE
DCOM- 20000504
LR  - 20220309
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 59
IP  - 11
DP  - 2000 Jun 1
TI  - Nrf2 and c-Jun regulation of antioxidant response element (ARE)-mediated 
      expression and induction of gamma-glutamylcysteine synthetase heavy subunit gene.
PG  - 1433-9
AB  - gamma-Glutamylcysteine synthetase (gamma-GCS) is a rate-limiting enzyme in the de 
      novo synthesis of glutathione, a known scavenger of electrophiles and reactive 
      oxygen species (ROS). The gamma-GCS gene is expressed ubiquitously and induced 
      coordinately with NAD(P)H:quinone oxidoreductase(1) (NQO1) and glutathione 
      S-transferase Ya (GST Ya) in response to xenobiotics and antioxidants. The 
      antioxidant response element (ARE) is required for expression and induction of 
      these genes. In the current report, we demonstrated that ARE-mediated gamma-GCS 
      gene expression and induction is regulated by similar Nrf and Jun factors as 
      reported earlier for the NQO1 and GST Ya genes. The gamma-GCS gene ARE competed 
      with the binding of nuclear proteins (Nrf + Jun) to the NQO1 gene ARE (hARE). In 
      addition, the overexpression of Nrf2 and Nrf1 with c-Jun significantly 
      up-regulated gamma-GCS ARE-mediated basal expression and beta-naphthoflavone 
      induction of the chloramphenicol acetyltransferase gene in transfected HepG2 
      cells. Interestingly, Nrf2 + c-Jun was more effective than Nrf1 + c-Jun in the 
      regulation of ARE-mediated gamma-GCS gene expression. Further experiments 
      demonstrated that the c-Jun level within the cells is an important determinant of 
      the level of ARE-mediated gamma-GCS gene expression. Therefore, at higher 
      concentrations of c-Jun, gamma-GCS gene expression is repressed, presumably due 
      to generation of a sufficient amount of c-Jun + c-Fos complex that interferes 
      with the binding of Nrf2 + c-Jun complex to the ARE.
FAU - Jeyapaul, J
AU  - Jeyapaul J
AD  - Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA.
FAU - Jaiswal, A K
AU  - Jaiswal AK
LA  - eng
GR  - GM47466/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antioxidants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Trans-Activators)
RN  - 9007-49-2 (DNA)
RN  - EC 1.6.5.11 (NADH dehydrogenase (quinone))
RN  - EC 1.6.99.- (Quinone Reductases)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Base Sequence
MH  - DNA/genetics/physiology
MH  - DNA-Binding Proteins/*physiology
MH  - Enzyme Induction
MH  - Glutamate-Cysteine Ligase/*biosynthesis/genetics
MH  - Glutathione Transferase/genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - NF-E2-Related Factor 2
MH  - Proto-Oncogene Proteins c-jun/*physiology
MH  - Quinone Reductases/genetics
MH  - Rats
MH  - Trans-Activators/*physiology
MH  - Tumor Cells, Cultured
EDAT- 2001/02/07 11:00
MHDA- 2001/02/07 11:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/02/07 11:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - S0006-2952(00)00256-2 [pii]
AID - 10.1016/s0006-2952(00)00256-2 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2000 Jun 1;59(11):1433-9. doi: 10.1016/s0006-2952(00)00256-2.