Expression of Glutathione and γ-Glutamylcysteine Synthetase mRNA Is Jun Dependent
| Autor: | Michael J. Meredith, Larry D. Kerr, Douglas R. Spitz, Zhi-Qi Xu, Michael L. Freeman, Konjeti R. Sekhar, Syrus R. Soltaninassab |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Proto-Oncogene Proteins c-jun
Glutamate-Cysteine Ligase Biophysics Biology Biochemistry Serine Mice chemistry.chemical_compound Okadaic Acid Tumor Cells Cultured Null cell Animals Humans RNA Messenger Molecular Biology Transcription factor Messenger RNA Wild type Cell Biology Okadaic acid Glutathione Molecular biology IκBα Gene Expression Regulation chemistry |
| Zdroj: | Biochemical and Biophysical Research Communications. 234:588-593 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.1997.6697 |
| Popis: | 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-kappaB and AP-1 activity. Inhibition of NF-kappaB activity by overexpression of an IkappaB alpha transdominant 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. |
| Databáze: | OpenAIRE |
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