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

Mulcahy, Ríona; Gipp, Jerry J.

doi:10.1006/bbrc.1995.1493

Cited by 183 publications

(88 citation statements)

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“…3). Although a TRE adjacent to EpRE was reported to be involved in regulation of catalytic subunit of glutamate cysteine ligase (GCLc) [49][50][51], it appears that adjacent TRE sites were not involved in basal or HNE-induced GP5 expression. In the gel-shift experiment, HNE treatment resulted in increased intensity of GP5 EpRE/ protein-binding complex, and this increase was concordant with the increased HNE responsiveness of the EpRE-driven constructs in the luciferase reporter assay.…”

Section: Discussionmentioning

confidence: 99%

“…EpRE/Nrf2 signaling has been found to be responsible for the induction of many phase II and antioxidant genes in response to ROS or electrophiles, including NADPH:quinine oxidoreductase-1 (NQO1) [80], HO-1 [81,82], glutamate cysteine ligase [35,[49][50][51], GSH Stransferase [83], and multidrug resistance protein [84]. Here we demonstrated that the induction of one major type of mRNA of GGT, a key enzyme involved in GSH homeostasis and GSH S-conjugates metabolism, is also mediated through EpRE/Nrf2 signaling in response to electrophile (HNE).…”

Section: Discussionmentioning

confidence: 99%

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γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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Abstractγ-Glutamyl transpeptidase (GGT) plays key roles in glutathione homeostasis and metabolism of glutathione S-conjugates. Rat GGT is transcribed via five tandemly arranged promoters into seven transcripts. The transcription of mRNAV is controlled by promoter 5. Previously we found that GGT mRNAV-2 was responsible for the induction of GGT in rat alveolar epithelial cells by 4-hydroxynonenal (HNE). In the current study, the underlying mechanism was investigated. Reporter deletion and mutation analysis demonstrated that an electrophile-response element (EpRE) in the proximal region of GGT promoter 5 (GP5) was responsible for the basal-and HNE-induced promoter activity. Gel-shift assays showed an increased binding activity of GP5 EpRE after HNE exposure. The nuclear content of NF-E2-related factor 2 (Nrf2) was significantly increased by HNE. The recruitment of Nrf2 to GP5 EpRE after HNE treatment was demonstrated by supershift and chromatin immunoprecipitation assays. The tissue expression pattern of GGT mRNA V was previously unknown. Using polymerase chain reaction, we found that GGT mRNAV-2 was expressed in many tissues in rat. Taken together, GGT mRNAV-2 is widely expressed in rat tissues and its basal and HNE-induced expression is mediated through EpRE/Nrf2 signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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“…15,16 In the present study, we directly posed the proofof-principle question regarding a role for JNK and its phosphorylation-dependent (serines 63,73) activation of transcription by c-jun of effector(s) in the acquired multidrug resistance phenotype of HL-60/ADR myeloid leukemia cells involving the aforementioned species. 1,16,38,39 We observed that overexpression of a dominant-negative (DN) nonphosphorylatable c-jun vector (JNP) resulted in down-regulation of two AP-1-regulated genes previously implicated in forms of multidrug resistance in other systems: 1,[14][15][16]38,40 catalase and GST (Figure 8). This appears to be one aspect of the outcome experienced in these cells with regard to their sensitivity to the anthracycline, daunorubicin.…”

Section: Discussionmentioning

confidence: 99%

Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia (AML): signaling to multidrug-efflux and hyperproliferation

Gelfanov

Smith

et al. 2002

Leukemia

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“…Since cis-regulatory elements including AP-l binding sites have been identified in the promoter regions of human γ -GCS and MRP1 genes (Mulcahy and Gipp, 1995;Yao et al, 1995;Zhu and Center, 1994) (Figure 9), it is extremely interesting to examine whether AP-1 is responsible for the transcriptional regulation of the expression of MRP1 and γ -GCS genes in cancer cells. Unlike cell culture studies where drug-resistant variants are usually obtained through continuous drug exposure, such transient induction of drug-resistance gene expression Figure 9.…”

Section: Coordinated Expression Of γ -Gcs and Mrp/gs-x Pumpmentioning

confidence: 99%

“…CRE, cyclic AMP response element; ERE, estrogen response element; GRE glucocorticoide response element, XRE, xenobiotic response elements, EpRE, Electrphile response element; CAT box, CCAAT box. Data from Zhu and Center, 1994;Yao et al, 1995;Mulcahy and Gipp, 1995. is more directly related to cancer chemotherapeutic protocols. Interestingly, human colorectal cancers frequently overexpress MRP1 and γ -GCS genes .…”

Section: Coordinated Expression Of γ -Gcs and Mrp/gs-x Pumpmentioning

confidence: 99%

A new aspect on glutathione-associated biological function of MRP/GS-X pump and its gene expression

Ishikawa¹,

Kuo²,

Furuta³

et al. 1998

Multiple Drug Resistance in Cancer 2

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The biological function as well as gene expression of the MRP/GS-X pump is closely linked with cellular GSH metabolism. This article describes two important aspects, i.e., 1) a role of the MRP/GS-X pump in the modulation of cell cycle arrest induced by anticancer prostaglandins; 2) coordinated up-regulation of γ -glutamylcysteine synthetase (γ -GCS) and MRP1 genes. The A and J series of prostaglandins (PGs) accumulate in the nuclei to suppress the proliferation of cancer cells. 7 -Prostaglandin A 1 ( 7 -PGA 1 ) methyl ester, a synthetic anticancer PG, increased the mRNA level of the cyclin-dependent kinase inhibitor p21 Sdi1/CI P 1/W AF 1 in human leukemia HL-60 cells. The induction of p21 Sdi1/CI P 1/W AF 1 was associated with the accumulation of hypophosphorylated retinoblastoma protein (pRB) and the suppression of c-myc gene expression. Unlike HL-60 cells, cisplatin-resistant HL-60/R-CP cells were insensitive to 7 -PGA 1 methyl ester. While c-myc expression was transiently suppressed, neither G1 arrest nor hypophosphorylation of pRB was observed with the anticancer PG. Plasma membrane vesicles from HL-60/R-CP cells showed an enhanced level of GS-X pump activity toward the glutathione Sconjugate of 7 -PGA 1 methyl ester. GIF-0019, a potent inhibitor of the GS-X pump, dose-dependently enhanced the cellular sensitivity of HL-60/R-CP cells to 7 -PGA 1 methyl ester, resulting in G1 arrest. The GS-X pump is suggested to play a pivotal role in modulating the biological action of the anticancer PG. The expression of MRP1 and γ -GCS genes can be coordinately up-regulated by cisplatin, 1-[5-(4-amino-2-methyl)pyrimidyl]methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), and heavy metals in human cancer cells. For the up-regulation of these genes, both transcriptional and posttranscriptional regulations are considered to be involved.

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

Cited by 183 publications

References 0 publications

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia (AML): signaling to multidrug-efflux and hyperproliferation

A new aspect on glutathione-associated biological function of MRP/GS-X pump and its gene expression

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