Interaction between glutathione and Cu(II) in the vicinity of nucleic acids
- 1 September 1994
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 302 (2), 373-382
- https://doi.org/10.1042/bj3020373
Abstract
GSH interacts with Cu(II) in the vicinity of DNA (pH approximately 7) to form the DNA-Cu(I) complex, which can be quantified by characteristic absorption changes [e.g. delta epsilon 295 = 4516 cm-1.M-1 Cu(I)]. Under initial conditions of Cu(II)/GSH >> 1 and DNA(base)/Cu(II) >> 5, the stoichiometry is 1 DNA-Cu(I) per SH group (also for other thiols). Stopped-flow kinetics show that the complex is formed with half-lives of 1-30 s, depending on the environment, but independent of O2. DNA-Cu(I) generation is much slower, less efficient, and O2-dependent at Cu(II)/GSH < 1, or when GSH interacts with Cu(II) before the addition of DNA. Interaction of GSH with Cu(II) in the presence of DNA [at Cu(II)/GSH > 1] leads to DNA-associated transients, probably DNA-GS(-)-Cu(I); DNA-Cu(I) formation under these conditions is proposed to occur by ligand exchange: DNA-GS(-)-Cu(I)+Cu(II)<-->DNA-Cu(I)+GS(-)-Cu(II). There is no evidence for generation of free thiyl radicals (GS.) on reaction of Cu(II) with GSH. Formation of DNA-Cu(I) is, in our opinion, a primary step involved in DNA-strand cleavage by GSH in the presence of Cu(II) [Reed and Douglas (1991) Biochem. J. 275, 601-608]. In this context the question of the pro-oxidative and/or antioxidative activity of GSH, when combined with copper, is discussed. GSH also generates Cu(I) complexes with other nucleic acids. An updated order of affinities of various nucleic acids for Cu(I) is presented. Cu(I) exhibits a high preference for alternating dG-dC sequences and might even be a Z-DNA inducer. The poly(C)-Cu(I) complex seems to form a base-paired structure at pH approximately 7, as demonstrated by intercalation of ethidium bromide.Keywords
This publication has 33 references indexed in Scilit:
- Interaction of Copper(I) with Nucleic AcidsInternational Journal of Radiation Biology, 1990
- Single-strand cleavage of DNA by Cu(II) and thiols: A powerful chemical DNA-cleaving systemBiochemical and Biophysical Research Communications, 1989
- Ferric and Cupric Ions Requirement for DNA Single-Strand Breakage by H2O2Free Radical Research Communications, 1989
- Copper-catalyzed dna damage by ascorbate and hydrogen peroxide: Kinetics and yieldFree Radical Biology & Medicine, 1987
- THE CHEMISTRY AND BIOLOGY OF LEFT-HANDED Z-DNAAnnual Review of Biochemistry, 1984
- The production of free radicals during the autoxidation of cysteine and their effect on isolated rat hepatocytesBiochimica et Biophysica Acta (BBA) - General Subjects, 1982
- Salt-induced co-operative conformational change of a synthetic DNA: Equilibrium and kinetic studies with poly(dG-dC)Journal of Molecular Biology, 1972
- A fluorescent complex between ethidium bromide and nucleic acidsJournal of Molecular Biology, 1967
- Influence of reductants upon optical characteristics of the DNA–Cu2+ complexBiopolymers, 1967
- Colorimetric measurement of cuprous ion formation to detect certain reducing agents as illustrated with cysteine, glutathione, and serum albuminBiochimica et Biophysica Acta, 1958