Journal article
Expression of Glutathione and γ-Glutamylcysteine Synthetase mRNA Is Jun Dependent
Biochemical and biophysical research communications, Vol.234(3), pp.588-593
05/29/1997
DOI: 10.1006/bbrc.1997.6697
PMID: 9175757
Abstract
The gene GLCLC encodes the catalytic subunit of gamma-glutamylcysteine synthetase (glutamate-cysteine ligase E.C. 6.3.2.2), the rate limiting enzyme for glutathione synthesis. When HepG2 cells were exposed to the serine/threonine phosphatase inhibitor okadaic acid (OA), increased expression of GLCLC was observed, as was the development of resistance to xenobiotic induced GSH depletion. Okadaic acid is known to activate both NF-κB and AP-1 activity. Inhibition of NF-κB activity by overexpression of an IκBα trans-dominant inhibitor or exposure to the protease inhibitor TLCK did not inhibit the OA mediated increase in GLCLC transcripts. Fibroblasts derived from a mouse containing a c-Jun null mutation exhibited diminished AP-1 binding activity, reduced levels of GLCLC message, and a correspondingly low GSH concentration compared to wild type cells. When the null cells, which express Jun B and Jun D, were exposed to OA, AP-1 binding activity increased, as did expression of GLCLC message. These results indicate that AP-1 transcription factors participate in the regulation of glutathione metabolism.
Details
- Title: Subtitle
- Expression of Glutathione and γ-Glutamylcysteine Synthetase mRNA Is Jun Dependent
- Creators
- Konjeti R. Sekhar - Vanderbilt UniversityMichael J. Meredith - Oregon Health & Science UniversityLarry D. Kerr - Vanderbilt UniversitySyrus R. Soltaninassab - Vanderbilt UniversityDouglas R. Spitz - Washington University in St. LouisZhi-Qi Xu - Vanderbilt UniversityMichael L. Freeman - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.234(3), pp.588-593
- Publisher
- Elsevier Inc
- DOI
- 10.1006/bbrc.1997.6697
- PMID
- 9175757
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Language
- English
- Date published
- 05/29/1997
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312981102771
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