Abstract

This project is based on the hypotheses that: (i) Spin trapping techniques can be used to identify low density lipoproteins (LDL) derived radicals and the spin traps may inhibit the oxidative modification of LDL; (ii) Free radical lipid peroxidation damages LDL as well as target macrophages and endothelial cells; (iii) Target cells utilize glutathione dependent selenoperoxidase(s) to detoxify LDL-lipid hydroperoxides (LDL-LOOHs).
Specific aims of the project are as follows: (i) Elucidate mechanisms of radical generation during LDL oxidation; (ii) Characterize lipid-derived radical intermediates; (iii) Study formation and enzymatic inactivation of LDL-LOOHs in non-cellular systems; and (iv) Study toxicity and selenoperoxidase mediated detoxification of LDL-derived LOOHs in cellular systems. Techniques to be used include: spin trapping, mass spectrometry, high performance liquid chromatography, and gel electrophoresis. This comprehensive investigation of the free radical aspects of LDL oxidation, together with the formation and metabolism of LOOH intermediates, is hoped to increase understanding of the chemistry of LDL oxidative modification.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL047250-04
Application #
2223520
Study Section
Pathology A Study Section (PTHA)
Project Start
1991-08-01
Project End
1995-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Medical College of Wisconsin
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226

  Publications

Kotamraju, S; Hogg, N; Joseph, J et al. (2001) Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide. Peroxyl radical scavenging as an antiapoptotic mechanism. J Biol Chem 276:17316-23
Zhang, H; Joseph, J; Vasquez-Vivar, J et al. (2000) Detection of superoxide anion using an isotopically labeled nitrone spin trap: potential biological applications. FEBS Lett 473:58-62
Shi, Y; Pritchard Jr, K A; Holman, P et al. (2000) Chronic myocardial hypoxia increases nitric oxide synthase and decreases caveolin-3. Free Radic Biol Med 29:695-703
Singh, R J; Hogg, N; Joseph, J et al. (1999) The peroxynitrite generator, SIN-1, becomes a nitric oxide donor in the presence of electron acceptors. Arch Biochem Biophys 361:331-9
Goss, S P; Hogg, N; Kalyanaraman, B (1999) The effect of alpha-tocopherol on the nitration of gamma-tocopherol by peroxynitrite. Arch Biochem Biophys 363:333-40
Singh, R J; Hogg, N; Goss, S P et al. (1999) Mechanism of superoxide dismutase/H(2)O(2)-mediated nitric oxide release from S-nitrosoglutathione--role of glutamate. Arch Biochem Biophys 372:8-15
Goss, S P; Singh, R J; Kalyanaraman, B (1999) Bicarbonate enhances the peroxidase activity of Cu,Zn-superoxide dismutase. Role of carbonate anion radical. J Biol Chem 274:28233-9
Ferguson, E; Hogg, N; Antholine, W E et al. (1999) Characterization of the adduct formed from the reaction between homocysteine thiolactone and low-density lipoprotein: antioxidant implications. Free Radic Biol Med 26:968-77
Hogg, N; Kalyanaraman, B (1999) Nitric oxide and lipid peroxidation. Biochim Biophys Acta 1411:378-84
Goss, S P; Singh, R J; Hogg, N et al. (1999) Reactions of *NO, *NO2 and peroxynitrite in membranes: physiological implications. Free Radic Res 31:597-606

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