Nitric oxide inhibition of free radical-mediated lipid peroxidation in photodynamically treated membranes and cells.
Of the numerous biological activities attributed to nitric oxide ((*)NO), relatively little is known about its ability to intercept lipid-derived free radicals and thus protect cells against the damaging effects of lipid peroxidation, particularly in photodynamic settings. To address this, we asked how the (*)NO donor spermine-NONOate (SPER/NO) would affect porphyrin (PpIX)-photosensitized, iron/ascorbate-amplified chain peroxidation in cholesterol (Ch)/phospholipid (0.8:1.0, mol/mol) liposomes. Several Ch oxidation products (ChOX) were monitored by high performance chromatographic techniques. When added immediately before irradiation, SPER/NO (0.4 mM) had no effect on accumulation of 5alpha-hydroperoxide, a primary singlet oxygen-derived ChOX, but strongly suppressed the secondary species arising from postphotooxidation chain reactions, including 7alpha/7beta-hydroperoxides, 7alpha/7beta-hydroxides, and 5,6-epoxides. Metabolism of exogenous 5-aminolevulinate to PpIX in COH-BR1 tumor cells sensitized them to ChOX photogeneration and necrotic photokilling. When present during irradiation, active (but not decomposed) SPER/NO strongly inhibited both effects. These findings support the hypothesis that suitably presented NO, by intercepting lipid-derived radicals, can antagonize the antitumor effects of photodynamic therapy and other oxidative therapies.
Niziolek
Magdalena
M
Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Korytowski
Witold
W
Girotti
Albert W
AW
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D004307:Dose-Response Relationship, Radiation; D005609:Free Radicals; D006801:Humans; D008027:Light; D015227:Lipid Peroxidation; D008081:Liposomes / Q000378:metabolism; D008956:Models, Chemical; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology
D005609:Free Radicals; D008081:Liposomes; D011166:Porphyrins; D009569:Nitric Oxide; D010100:Oxygen