Protective role of metallothionein against copper depletion.
Copper (Cu) is one of the essential metals and its homeostasis is strictly regulated. Metallothionein (MT) is induced by excess Cu to mask the Cu toxicity. Although the role of MT in Cu toxicity has been explained in terms of Cu sequestration, its role under Cu-deficient conditions is not known. This study was carried out to determine the role of MT in Cu depletion by a Cu(I)-specific chelator, bathocuproine sulfonate (BCS), in cultured cells established from MT-knockout mouse and its wild type. Viability was decreased more severely in MT-null cells than in wild-type cells by BCS treatment. The expression levels of both MT isoforms were increased by BCS treatment in wild-type cells. Thus, MT was shown to be induced under Cu-deficient conditions to maintain the activities of intracellular cuproenzymes such as cytochrome c oxidase and Cu,zinc-superoxide dismutase.
Ogra
Yasumitsu
Y
Department of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Aoyama
Mariko
M
Suzuki
Kazuo T
KT
D000818:Animals; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000172:deficiency* / Q000378:metabolism* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000032:analysis / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010618:Phenanthrolines / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D002614:Chelating Agents; D010618:Phenanthrolines; D020033:Protein Isoforms; C028559:bathocuproine sulfonate; D003300:Copper; D008668:Metallothionein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003576:Electron Transport Complex IV