Abstract
Mutation analysis of putative regulatory elements located in the 5'-flanking region of the gene encoding the regulatory subunit of gamma-glutamylcysteine synthetase (GLCLR) revealed that neither an antioxidant-responsive element (ARE) nor an activator protein-1 (AP-1) site regulates inducible expression by t-butylhydroquinone (tBHQ). The AP-1 site was found to modulate basal expression of GLCLR. A 42 bp region between nucleotides -303 and -344, not containing an ARE, was found to regulate inducible expression of GLCLR by tBHQ.
Full Text
The Full Text of this article is available as a PDF (154.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cai J., Huang Z. Z., Lu S. C. Differential regulation of gamma-glutamylcysteine synthetase heavy and light subunit gene expression. Biochem J. 1997 Aug 15;326(Pt 1):167–172. doi: 10.1042/bj3260167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chasseaud L. F. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv Cancer Res. 1979;29:175–274. doi: 10.1016/s0065-230x(08)60848-9. [DOI] [PubMed] [Google Scholar]
- Dalton T. P., Li Q., Bittel D., Liang L., Andrews G. K. Oxidative stress activates metal-responsive transcription factor-1 binding activity. Occupancy in vivo of metal response elements in the metallothionein-I gene promoter. J Biol Chem. 1996 Oct 18;271(42):26233–26241. doi: 10.1074/jbc.271.42.26233. [DOI] [PubMed] [Google Scholar]
- Galloway D. C., Blake D. G., Shepherd A. G., McLellan L. I. Regulation of human gamma-glutamylcysteine synthetase: co-ordinate induction of the catalytic and regulatory subunits in HepG2 cells. Biochem J. 1997 Nov 15;328(Pt 1):99–104. doi: 10.1042/bj3280099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henikoff S. Unidirectional digestion with exonuclease III in DNA sequence analysis. Methods Enzymol. 1987;155:156–165. doi: 10.1016/0076-6879(87)55014-5. [DOI] [PubMed] [Google Scholar]
- Higuchi R., Krummel B., Saiki R. K. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 1988 Aug 11;16(15):7351–7367. doi: 10.1093/nar/16.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang C. S., Anderson M. E., Meister A. Amino acid sequence and function of the light subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem. 1993 Sep 25;268(27):20578–20583. [PubMed] [Google Scholar]
- Huang C. S., Chang L. S., Anderson M. E., Meister A. Catalytic and regulatory properties of the heavy subunit of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem. 1993 Sep 15;268(26):19675–19680. [PubMed] [Google Scholar]
- Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
- Meister A. Glutathione metabolism and its selective modification. J Biol Chem. 1988 Nov 25;263(33):17205–17208. [PubMed] [Google Scholar]
- Moinova H. R., Mulcahy R. T. An electrophile responsive element (EpRE) regulates beta-naphthoflavone induction of the human gamma-glutamylcysteine synthetase regulatory subunit gene. Constitutive expression is mediated by an adjacent AP-1 site. J Biol Chem. 1998 Jun 12;273(24):14683–14689. doi: 10.1074/jbc.273.24.14683. [DOI] [PubMed] [Google Scholar]
- Morales A., García-Ruiz C., Miranda M., Marí M., Colell A., Ardite E., Fernández-Checa J. C. Tumor necrosis factor increases hepatocellular glutathione by transcriptional regulation of the heavy subunit chain of gamma-glutamylcysteine synthetase. J Biol Chem. 1997 Nov 28;272(48):30371–30379. doi: 10.1074/jbc.272.48.30371. [DOI] [PubMed] [Google Scholar]
- Mulcahy R. T., Wartman M. A., Bailey H. H., Gipp J. J. Constitutive and beta-naphthoflavone-induced expression of the human gamma-glutamylcysteine synthetase heavy subunit gene is regulated by a distal antioxidant response element/TRE sequence. J Biol Chem. 1997 Mar 14;272(11):7445–7454. doi: 10.1074/jbc.272.11.7445. [DOI] [PubMed] [Google Scholar]
- Rahman I., Bel A., Mulier B., Lawson M. F., Harrison D. J., Macnee W., Smith C. A. Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells. Biochem Biophys Res Commun. 1996 Dec 24;229(3):832–837. doi: 10.1006/bbrc.1996.1888. [DOI] [PubMed] [Google Scholar]
- Rahman I., Smith C. A., Lawson M. F., Harrison D. J., MacNee W. Induction of gamma-glutamylcysteine synthetase by cigarette smoke is associated with AP-1 in human alveolar epithelial cells. FEBS Lett. 1996 Oct 28;396(1):21–25. doi: 10.1016/0014-5793(96)01027-7. [DOI] [PubMed] [Google Scholar]
- Richman P. G., Meister A. Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem. 1975 Feb 25;250(4):1422–1426. [PubMed] [Google Scholar]
- Rushmore T. H., Morton M. R., Pickett C. B. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem. 1991 Jun 25;266(18):11632–11639. [PubMed] [Google Scholar]
- Seelig G. F., Meister A. Glutathione biosynthesis; gamma-glutamylcysteine synthetase from rat kidney. Methods Enzymol. 1985;113:379–390. doi: 10.1016/s0076-6879(85)13050-8. [DOI] [PubMed] [Google Scholar]
- Sekhar K. R., Long M., Long J., Xu Z. Q., Summar M. L., Freeman M. L. Alteration of transcriptional and post-transcriptional expression of gamma-glutamylcysteine synthetase by diethyl maleate. Radiat Res. 1997 May;147(5):592–597. [PubMed] [Google Scholar]
- Sekhar K. R., Meredith M. J., Kerr L. D., Soltaninassab S. R., Spitz D. R., Xu Z. Q., Freeman M. L. Expression of glutathione and gamma-glutamylcysteine synthetase mRNA is Jun dependent. Biochem Biophys Res Commun. 1997 May 29;234(3):588–593. doi: 10.1006/bbrc.1997.6697. [DOI] [PubMed] [Google Scholar]
- Shi M. M., Iwamoto T., Forman H. J. gamma-Glutamylcysteine synthetase and GSH increase in quinone-induced oxidative stress in BPAEC. Am J Physiol. 1994 Oct;267(4 Pt 1):L414–L421. doi: 10.1152/ajplung.1994.267.4.L414. [DOI] [PubMed] [Google Scholar]
- Shi M. M., Kugelman A., Iwamoto T., Tian L., Forman H. J. Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells. J Biol Chem. 1994 Oct 21;269(42):26512–26517. [PubMed] [Google Scholar]
- Tomonari A., Nishio K., Kurokawa H., Arioka H., Ishida T., Fukumoto H., Fukuoka K., Nomoto T., Iwamoto Y., Heike Y. Identification of cis-acting DNA elements of the human gamma-glutamylcysteine synthetase heavy subunit gene. Biochem Biophys Res Commun. 1997 Mar 17;232(2):522–527. doi: 10.1006/bbrc.1997.6319. [DOI] [PubMed] [Google Scholar]
- Yan N., Meister A. Amino acid sequence of rat kidney gamma-glutamylcysteine synthetase. J Biol Chem. 1990 Jan 25;265(3):1588–1593. [PubMed] [Google Scholar]