Specific induction of metallothionein synthesis by mitochondrial oxidative stress

Metallothionein (MT), a sulfhydryl-rich protein, may be increased by administration of a variety of agents, including metals, cytokines and oxidative stress agents. Mitochondria are a major source of reactive oxygen species, but antioxidant systems against mitochondrial free radicals are not fully u...

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Bibliographic Details
Published in:Life sciences (1973) 2001-09, Vol.69 (18), p.2137-2146
Main Authors: Kondoh, Masuo, Inoue, Yuko, Atagi, Saori, Futakawa, Naoki, Higashimoto, Minoru, Sato, Masao
Format: Article
Language:English
Subjects:
2,4-Dinitrophenol
2,4-Dinitrophenol - pharmacology
Animals
Antimycin A
Antimycin A - analogs & derivatives
Antimycin A - pharmacology
Male
Metallothionein
Metallothionein - biosynthesis
Mice
Mitochondria
Mitochondria - metabolism
Oxidative Stress
Reactive Oxygen Species - metabolism
Uncoupling Agents - pharmacology
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Summary:Metallothionein (MT), a sulfhydryl-rich protein, may be increased by administration of a variety of agents, including metals, cytokines and oxidative stress agents. Mitochondria are a major source of reactive oxygen species, but antioxidant systems against mitochondrial free radicals are not fully understood. In this study, we examined the induction of MT synthesis by administration of mitochondrial-specific reactive oxygen generators such as antimycin A (AA), an electron transfer inhibitor, and 2,4-dinitrophenol (DNP), an uncoupling agent. Subcutaneous administration of AA to mice significantly increased the hepatic MT concentration in a dose- and time-dependent manner. AA slightly elevated glutathione peroxidase (GSHPx) activity, but the rate of increase in GSHPx (1.3-fold) was smaller than that in MT (11.8-fold). Other antioxidants such as catalase, manganese-superoxide dismutase (Mn-SOD), copper/zinc-superoxide dismutase (Cu/Zn-SOD) and GSHPx were not activated by AA treatment. Moreover, administration of DNP induced the synthesis of MT in the liver. Although DNP slightly elevated Mn-SOD activity, the rate of increase in Mn-SOD (1.3-fold) was smaller than that in MT (3.7-fold). Other antioxidants such as catalase, Cu/Zn-SOD and GSHPx were not activated by DNP treatment. These data suggest that MT plays a major role in protection against oxidative stress induced in mitochondria.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(01)01294-2