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Titolo:
DITHIOCARBAMATES INDUCE APOPTOSIS IN THYMOCYTES BY RAISING THE INTRACELLULAR LEVEL OF REDOX-ACTIVE COPPER
Autore:
NOBEL CSI; KIMLAND M; LIND B; ORRENIUS S; SLATER AFG;
Indirizzi:
KAROLINSKA INST,INST ENVIRONM MED,DIV TOXICOL,BOX 210 S-17177 STOCKHOLM SWEDEN KAROLINSKA INST,INST ENVIRONM MED,DIV TOXICOL S-17177 STOCKHOLM SWEDEN KAROLINSKA INST,DIV MET & HLTH S-17177 STOCKHOLM SWEDEN
Titolo Testata:
The Journal of biological chemistry
fascicolo: 44, volume: 270, anno: 1995,
pagine: 26202 - 26208
SICI:
0021-9258(1995)270:44<26202:DIAITB>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTACT-CELLS; SERUM COPPER; KAPPA-B; DIETHYLDITHIOCARBAMATE; GLUTATHIONE; TOXICITY; METABOLISM; DISULFIDES; PROTECTION; ACTIVATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
49
Recensione:
Indirizzi per estratti:
Citazione:
C.S.I. Nobel et al., "DITHIOCARBAMATES INDUCE APOPTOSIS IN THYMOCYTES BY RAISING THE INTRACELLULAR LEVEL OF REDOX-ACTIVE COPPER", The Journal of biological chemistry, 270(44), 1995, pp. 26202-26208

Abstract

Dithiocarbamates are metal-chelating compounds that can exert either pro-oxidant or antioxidant effects in different situations, They have recently been found to potently inhibit apoptotic cell death, an activity attributed to their antioxidant action, However, when thymocytes were exposed to pyrrolidine dithiocarbamate, an oxidation of the glutathione pool occurred within 90 min, Longer incubation resulted in cell shrinkage, chromatin fragmentation, glutathione depletion, and eventual cell lysis, which is typical of apoptosis in these cells, These changes were inhibited by inclusion of non-permeable metal chelators in the incubation medium, suggesting that pyrrolidine dithiocarbamate exerts its toxic effect by transporting a redox-active metal into the cell. This was directly confirmed when sustained 8-fold elevations of intracellular copper were detected after addition of pyrrolidine dithiocarbamate. In agreement with this, supplementation of the incubation medium with submicromolar concentrations of copper significantly potentiated pyrrolidine dithiocarbamate toxicity, We conclude that pyrrolidine dithiocarbamate exerts a powerful pro oxidant effect on thymocytes due to its ability to transport external redox-active copper into cells, The resulting increase in glutathione disulfide may also explain the temporary anti-apoptotic activity of this compound described in other systems.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 19:23:32