Biologically active metal-independent superoxide dismutase mimics

Journal Article · Tue Mar 20 04:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00463a024· OSTI ID:6714379

Mitchell, J B; Samuni, A; Krishna, M C; DeGraff, W G; Ahn, M S; Samuni, U; Russo, A ^[1]

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1. National Cancer Institute, National Institutes of Health, Bethesda, MD (USA)

Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H{sub 2}O{sub 2}, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.

• OSTI ID: 6714379
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:11; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL FUNCTIONS
CELL CULTURES
CHEMICAL REACTIONS
CYTOCHROMES
DNA
ELECTRON SPIN RESONANCE
ENZYMES
FUNCTIONS
HAMSTERS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
MAGNETIC RESONANCE
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
PIGMENTS
PROTEINS
REDOX REACTIONS
RESONANCE
RODENTS
SUPEROXIDE DISMUTASE
TOXICITY
VERTEBRATES