Abstract

Krishna et al (Proc. Natl. Acad. Sci. USA 89:5537-5541, 1992) showed that nitroxides act as superoxide disumate (SOD) mimetics but are oxidized to the oxoammonium instead of reduced to the hydroxylamine (as they previously stated, Samuni et al (J. Biol. Chem. 263:17921-17924, 1988). Our data supports their more recent conclusions. In our mechanism, TEMPOL is reduced by two mechanisms, 1) by one electron reduction via the electron transport system and 2) by two electron reduction from the oxoammonium ion produced by SOD-like activity of the nitroxide. Peroxide re-oxidizes the hydroxylamine to the nitroxide and plays a major role in determinin g overall nitroxide reduction rates. Catalase activity in the 983.2 cells is only 5% of that in the BHK cells which may allow excess peroxide to recycle the hydroxylamine back to the nitroxide. This would explain the lower overall TEMPOL reduction rates seen in 983.2 cells compared to BHK cells. Our model and the evidence in support of it was presented in detail during 1995. Supported by NIH grants R15 GM 44365-01 to PDM and R15 CA52091-01A1 to LAL.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR001811-11
Application #
5223635
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Hurth, Kyle M; Nilges, Mark J; Carlson, Kathryn E et al. (2004) Ligand-induced changes in estrogen receptor conformation as measured by site-directed spin labeling. Biochemistry 43:1891-907
Woodmansee, Anh N; Imlay, James A (2002) Reduced flavins promote oxidative DNA damage in non-respiring Escherichia coli by delivering electrons to intracellular free iron. J Biol Chem 277:34055-66
Denisov, Ilia G; Makris, Thomas M; Sligar, Stephen G (2002) Formation and decay of hydroperoxo-ferric heme complex in horseradish peroxidase studied by cryoradiolysis. J Biol Chem 277:42706-10
Atsarkin, V A; Demidov, V V; Vasneva, G A et al. (2001) Mechanism of oxygen response in carbon-based sensors. J Magn Reson 149:85-9
Mangels, M L; Harper, A C; Smirnov, A I et al. (2001) Investigating magnetically aligned phospholipid bilayers with EPR spectroscopy at 94 GHz. J Magn Reson 151:253-9
Breitzer, J G; Smirnov, A I; Szczepura, L F et al. (2001) Redox properties of C6S8(n-) and C3S5(n-) (n = 0, 1, 2): stable radicals and unusual structural properties for C-S-S-C bonds. Inorg Chem 40:1421-9
Denisov, I G; Hung, S C; Weiss, K E et al. (2001) Characterization of the oxygenated intermediate of the thermophilic cytochrome P450 CYP119. J Inorg Biochem 87:215-26
Kirkor, E S; Scheeline, A (2000) Nicotinamide adenine dinucleotide species in the horseradish peroxidase-oxidase oscillator. Eur J Biochem 267:5014-22
Rapoport, N; Smirnov, A I; Pitt, W G et al. (1999) Bioreduction of Tempone and spin-labeled gentamicin by gram-negative bacteria: kinetics and effect of ultrasound. Arch Biochem Biophys 362:233-41
Maringanti, S; Imlay, J A (1999) An intracellular iron chelator pleiotropically suppresses enzymatic and growth defects of superoxide dismutase-deficient Escherichia coli. J Bacteriol 181:3792-802

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