Interactions of platinum complexes with thioltransferase(glutaredoxin), in vitro.
Under anaerobic conditions, recombinant pig liver thioltransferase (glutaredoxin)(TT, GRX) (EC 1.8.4.1) was strongly inhibited by cis and carbo-platin and somewhat less sensitive to trans-platin, in vitro. By extrapolation to total inhibition, the ratio of platinum drug/thioltransferase was approximately 1.0 for cis and carbo-platin, but greater than 1.0 for trans-platin. When thioltransferase was not reduced, inhibition by preincubation with the platinum complexes required molar excesses of 1,300 and 675 to one for cis-platin and trans-platin, respectively or 400-500 microM for 50% inhibition. The inhibition of thioltransferase at high drug concentrations in the presence of oxygen was associated with cross-linking of monomers into dimers within 5 min and, in the case of cis-platin treatment, to trimers in 20 min incubation.
Wells
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WW
Department of Biochemistry, Michigan State University, East Lansing 48824.
Rocque
P A
PA
Xu
D P
DP
Yang
Y
Y
Deits
T L
TL
D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D054477:Glutaredoxins; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D046911:Macromolecular Substances; D008970:Molecular Weight; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011490:Protein Disulfide Reductase (Glutathione); D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine
D000970:Antineoplastic Agents; D054477:Glutaredoxins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; C034697:transplatin; D016190:Carboplatin; D010088:Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione); D002945:Cisplatin