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Effect of glutathione depletion on metallothionein synthesis induced by paraquat in mice
- Source :
- The Tohoku journal of experimental medicine. 177(3)
- Publication Year :
- 1995
-
Abstract
- The effect of Glutathione (GSH) depletion on the induction of metallothionein (MT) synthesis by paraquat (PQ) was examined in ICR mice. An increase in hepatic MT level in mice was observed after a single PQ administration. Pretreatment of mice with L-buthionine-SR-sulfoximine (BSO), an inhibitor of GSH synthesis, enhanced the induction of hepatic and renal MT synthesis by PQ depending on the decreased tissue GSH level. A similar result was obtained by pretreatment with diethylmaleate, a GSH depleting agent. The ratio of hepatic MT-I to MT-II induced by PQ was not changed by BSO pretreatment. An increase in the hepatic MT level in GSH depleted mice was observed from 3 hr to 24 hr after PQ administration. An increase in the hepatic MT-I mRNA level after treatment with PQ was observed prior to hepatic MT induction in BSO pretreated mice. Pretreatment with actinomycin D, an inhibitor of mRNA synthesis, inhibits the PQ-induced increase in hepatic MT and MT-I mRNA levels in BSO pretreated mice. Pretreatment with BSO did not affect the induction of MT synthesis by zinc, cadmium or dexamethasone. Pretreatment with dexamethasone, an anti-inflammatory agent, enhanced the hepatic MT induction by PQ treatment in GSH depleted mice, while dexamethasone reduced the MT induction by turpentine oil, which is known to induce inflammation and hepatic MT synthesis. These findings suggest that GSH depletion enhances the induction of MT synthesis by PQ because of an increase in the transcription rate, and this enhancement of MT synthesis is not due to an inflammatory response caused by PQ.
- Subjects :
- Male
Paraquat
MRNA synthesis
Antimetabolites
Inflammation
Pharmacology
Kidney
General Biochemistry, Genetics and Molecular Biology
Dexamethasone
chemistry.chemical_compound
Mice
Chlorides
medicine
Metallothionein
Animals
Buthionine Sulfoximine
Glucocorticoids
Protein Synthesis Inhibitors
Mice, Inbred ICR
Herbicides
Maleates
General Medicine
Glutathione
Blotting, Northern
Chromatography, Ion Exchange
chemistry
Mrna level
Liver
Zinc Compounds
Chromatography, Gel
Dactinomycin
medicine.symptom
Icr mice
medicine.drug
Cadmium
Subjects
Details
- ISSN :
- 00408727
- Volume :
- 177
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- The Tohoku journal of experimental medicine
- Accession number :
- edsair.doi.dedup.....31b320279b267ae3296e9396f9130195