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Effect of Metal Complexes on Thioredoxin Reductase and the Regulation of Mitochondrial Permeability Conditions
Author(s) -
BRAGADIN M,
SCUTARI G,
FOLDA A,
BINDOLI A,
RIGOBELLO M P
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.043
Subject(s) - thioredoxin reductase , auranofin , chemistry , gold compounds , thioredoxin , reductase , glutathione , membrane permeability , mitochondrial permeability transition pore , metal , mitochondrial respiratory chain , biochemistry , mitochondrion , membrane , enzyme , organic chemistry , combinatorial chemistry , biology , apoptosis , programmed cell death , immunology , rheumatoid arthritis
A bstract : Gold(I) compounds such as auranofin, chloro(triethylphosphine) gold(I), and aurothiomalate act on mitochondrial functional parameters by determining an extensive permeability transition and a decrease of membrane potential. On the contrary, pyridine nucleotides and glutathione are not modified, whereas a slight but significant decrease of total thiols is apparent. The effect of gold(I) compounds is essentially referable to the inhibition, in the nanomolar range, of thioredoxin reductase activity and to an increase of hydrogen peroxide production. Metal ions and metal complexes (zinc and cadmium acetate, cisplatin, tributyltin) are also good inhibitors of thioredoxin reductase, although in the micromolar range, and in addition, they act as inducers of permeability transition and of membrane potential decrease. At variance with gold(I) compounds, which appear to work almost exclusively on thioredoxin reductase, metal ions and complexes are less specific, since they are active on different mitochondrial targets, including the respiratory chain.