gamma-glutamylcysteine synthetase: mRNA stabilization and independent subunit transcription by 4-hydroxy-2-nonenal
- PMID: 9815102
- DOI: 10.1152/ajplung.1998.275.5.L861
gamma-glutamylcysteine synthetase: mRNA stabilization and independent subunit transcription by 4-hydroxy-2-nonenal
Abstract
gamma-Glutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo glutathione (GSH) synthesis, is composed of one catalytic (heavy) and one regulatory (light) subunit. Although both subunits are increased at the mRNA level by oxidants, it is not clear whether they are regulated through the same mechanism. 4-Hydroxy-2-nonenal (4HNE), a lipid peroxidation product, may act as a mediator for the induction of gene expression by oxidants. In the present study, 4HNE was used to study the mechanism of induction of the two GCS subunits in rat lung epithelial L2 cells. 4HNE increased both the transcription rates and the stability of mRNA for both GCS subunits, resulting in an increased mRNA content for both subunits. Both GCS subunit proteins and enzymatic activities also increased. Emetine, a protein synthesis inhibitor, blocked the increase in GCS light subunit mRNA but not the increase in GCS heavy subunit mRNA. This suggested that although 4HNE increased transcription and stabilization of both GCS subunit mRNAs, the signaling pathways involved in the induction of the two GCS subunits differed.
Similar articles
-
4-Hydroxy-2-nonenal increases gamma-glutamylcysteine synthetase gene expression in alveolar epithelial cells.Am J Respir Cell Mol Biol. 2001 Apr;24(4):499-505. doi: 10.1165/ajrcmb.24.4.4307. Am J Respir Cell Mol Biol. 2001. PMID: 11306445
-
Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion.Arch Biochem Biophys. 1997 Jun 1;342(1):126-33. doi: 10.1006/abbi.1997.9997. Arch Biochem Biophys. 1997. PMID: 9185621
-
Differential enhancement of gamma-glutamyl transpeptidase and gamma-glutamylcysteine synthetase by tert-butylhydroquinone in rat lung epithelial L2 cells.Am J Respir Cell Mol Biol. 1996 Feb;14(2):186-91. doi: 10.1165/ajrcmb.14.2.8630269. Am J Respir Cell Mol Biol. 1996. PMID: 8630269
-
Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defenses.Free Radic Res. 2000 Apr;32(4):281-301. doi: 10.1080/10715760000300291. Free Radic Res. 2000. PMID: 10741850 Review.
-
Regulation of gamma-glutamylcysteine synthetase expression in response to oxidative stress.Free Radic Res. 1999 Oct;31(4):325-34. doi: 10.1080/10715769900300891. Free Radic Res. 1999. PMID: 10517537 Review.
Cited by
-
Age-related changes in glutathione and glutathione-related enzymes in rat brain.Brain Res. 2006 May 23;1090(1):35-44. doi: 10.1016/j.brainres.2006.03.063. Epub 2006 May 2. Brain Res. 2006. PMID: 16647047 Free PMC article.
-
Afferent regulation of oxidative stress in the chick cochlear nucleus.Neuroscience. 2006 Jul 21;140(4):1359-68. doi: 10.1016/j.neuroscience.2006.03.015. Epub 2006 May 2. Neuroscience. 2006. PMID: 16650604 Free PMC article.
-
4-Hydroxynonenal increases gamma-glutamyl transpeptidase gene expression through mitogen-activated protein kinase pathways.Free Radic Biol Med. 2005 Feb 15;38(4):463-71. doi: 10.1016/j.freeradbiomed.2004.10.031. Free Radic Biol Med. 2005. PMID: 15649648 Free PMC article.
-
Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase.Mol Aspects Med. 2009 Feb-Apr;30(1-2):86-98. doi: 10.1016/j.mam.2008.08.009. Epub 2008 Sep 6. Mol Aspects Med. 2009. PMID: 18812186 Free PMC article. Review.
-
4-Hydroxy-Trans-2-Nonenal in the Regulation of Anti-Oxidative and Pro-Inflammatory Signaling Pathways.Oxid Med Cell Longev. 2019 Nov 6;2019:5937326. doi: 10.1155/2019/5937326. eCollection 2019. Oxid Med Cell Longev. 2019. PMID: 31781341 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
