Identification of a Putative Antioxidant Response Element in the 5′-Flanking Region of the Human γ-Glutamylcysteine Synthetase Heavy Subunit Gene

1995 ◽  
Vol 209 (1) ◽  
pp. 227-233 ◽  
Author(s):  
R.T. Mulcahy ◽  
J.J. Gipp
Keyword(s):  
Antioxidant Response ◽  
Antioxidant Response Element ◽  
Subunit Gene ◽  
Response Element ◽  
Glutamylcysteine Synthetase ◽  
Flanking Region

scholarly journals Overlapping antioxidant response element and PMA responseelement sequences mediate basal and β-naphthoflavone-induced expression of the human γ-glutamylcysteine synthetase catalytic subunit gene

1998 ◽  
Vol 332 (2) ◽  
pp. 373-381 ◽  
Author(s):  
Angela C. WILD ◽  
Jerry J. GIPP ◽  
R. Timothy MULCAHY
Keyword(s):  
Hepg2 Cells ◽  
Constitutive Expression ◽  
Antioxidant Response ◽  
Regulatory Subunit ◽  
Antioxidant Response Element ◽  
Induced Expression ◽  
Response Element ◽  
Relative Significance ◽  
Glutamylcysteine Synthetase ◽  
Gc Box

γ-Glutamylcysteine synthetase (GCS), the rate-limiting enzyme in the de novo synthesis of GSH, is a heterodimer, consisting of a catalytic (GCSh) and a regulatory subunit (GCSl). We previously demonstrated that the constitutive and β-naphthoflavone (β-NF)-induced expression of the GCSh gene is mediated by a distal antioxidant response element (ARE), ARE4, located 3.1 kb upstream of the transcriptional start site [Mulcahy, Wartman, Bailey and Gipp (1997) J. Biol. Chem. 272, 7445–7454]. ARE4 consists of a consensus ARE sequence (5´-GTGACTCAGCG-3´) containing an embedded PMA-responsive element (TRE, underlined). The relative significance of the two overlapping response elements to constitutive and β-NF-induced expression of the GCSh gene was determined by mutational analyses. The internal activator protein-1 (AP-1)-binding sequence mediated constitutive expression of promoter/reporter transgenes, but was not required for β-NF responsiveness. In gel-shift experiments, the TRE was necessary for binding of proteins from nuclear extracts prepared from untreated HepG2 cells. In contrast, induction by β-NF was dependent on an intact ARE sequence, particularly the terminal GC box of ARE4. The GC box of ARE4 was shown to be essential for both basal and β-NF-induced expression of reporter constructs. This element also influenced binding of nuclear proteins to ARE4, specifically in extracts isolated from β-NF-treated HepG2 cells. Because previous studies indicated that ARE4 may co-operate with a separate putative ARE, the role of the neighbouring sequence (ARE3), located 34 bases downstream of ARE4, was also evaluated. Mutation of this element within a GCSh promoter/reporter did not modify the basal or β-NF-induced expression of the transgene, demonstrating that ARE3 does not influence the constitutive or β-NF-induced expression of the GCSh gene.

scholarly journals Induction of the Protective Antioxidant Response Element Pathway by 6-Hydroxydopamine In Vivo and In Vitro

2005 ◽  
Vol 87 (1) ◽  
pp. 176-186 ◽  
Author(s):  
Rebekah J. Jakel ◽  
Jonathan T. Kern ◽  
Delinda A. Johnson ◽  
Jeffrey A. Johnson
Keyword(s):  
Antioxidant Response ◽  
Antioxidant Response Element ◽  
Response Element ◽  
6 Hydroxydopamine

scholarly journals Homocysteine stimulates antioxidant response element-mediated expression of glutamate-cysteine ligase in mouse macrophages

2009 ◽  
Vol 203 (1) ◽  
pp. 105-111 ◽  
Author(s):  
Florian Bea ◽  
Francesca N. Hudson ◽  
Haley Neff-LaFord ◽  
Collin C. White ◽  
Terrance J. Kavanagh ◽  
...  
Keyword(s):  
Antioxidant Response ◽  
Antioxidant Response Element ◽  
Glutamate Cysteine Ligase ◽  
Response Element ◽  
Mouse Macrophages
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