Formation of phospholipid hydroperoxides and its inhibition by alpha-tocopherol in rat brain synaptosomes induced by peroxynitrite.

Peroxynitrite resulted from the reaction of nitric oxide and superoxide anion has been implicated in the genesis of neurotoxicity. In this study, the oxidation of phospholipids in rat brain synaptosomes induced by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1) was studied in vitro. The formation and accumulation of phospholipid hydroperoxides, including phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl-ethanolamine hydroperoxide (PEOOH) in rat brain synaptosomes induced by peroxynitrite, were observed. PEOOH and PCOOH were formed rapidly and SIN-1 concentration-dependently. The hydroperoxides formed in synaptosomes were unstable and it was suggested that phospholipase A2 played a role in degradation of the hydroperoxides. The endogenous alpha-tocopherol acted as a potent antioxidant. It was oxidized very rapidly and concentration-dependently by SIN-1 to alpha-tocopheryl quinone. Furthermore, uric acid was found to be an effective antioxidant in inhibiting oxidative damage to synaptosomal lipids induced by SIN-1. The results provide direct evidence to show that peroxynitrite can not only deplete alpha-tocopherol, but also cause production of phospholipid hydroperoxides resulting in disrupted brain tissue.

[1]  Yoshimasa Nakamura,et al.  Activation of Stress Signaling Pathways by the End Product of Lipid Peroxidation , 1999, The Journal of Biological Chemistry.

[2]  V. Darley-Usmar,et al.  Nitrosation of Uric Acid by Peroxynitrite , 1998, The Journal of Biological Chemistry.

[3]  W. Pryor,et al.  Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide. , 1998, Free radical biology & medicine.

[4]  A. Girotti.  Lipid hydroperoxide generation, turnover, and effector action in biological systems. , 1998, Journal of lipid research.

[5]  B. Kalyanaraman,et al.  Nitric oxide and low-density lipoprotein oxidation. , 1998, Free radical research.

[6]  R. Stocker,et al.  Oxidation and antioxidation of human low-density lipoprotein and plasma exposed to 3-morpholinosydnonimine and reagent peroxynitrite. , 1998, Chemical research in toxicology.

[7]  G. Vatassery,et al.  Oxidation of cholesterol in synaptosomes and mitochondria isolated from rat brains , 1997, Lipids.

[8]  K. Kristensson,et al.  The lipid compositions of different regions of rat brain during development and aging , 1996, Neurobiology of Aging.

[9]  G. Vatassery.  Oxidation of vitamin E, vitamin C, and thiols in rat brain synaptosomes by peroxynitrite. , 1996, Biochemical pharmacology.

[10]  S. Prusiner,et al.  Lipid Composition in Scrapie‐Infected Mouse Brain: Prion Infection Increases the Levels of Dolichyl Phosphate and Ubiquinone , 1996, Journal of neurochemistry.

[11]  T. Kaneko,et al.  Cytotoxicity of phosphatidylcholine hydroperoxides is exerted through decomposition of fatty acid hydroperoxide moiety. , 1996, Free radical biology & medicine.

[12]  J. Coyle,et al.  Oxidative stress in neurodegenerative diseases. , 1996, Annual review of pharmacology and toxicology.

[13]  S. Kawanishi,et al.  Oxidative DNA damage induced by simultaneous generation of nitric oxide and superoxide , 1995, FEBS letters.

[14]  J. Joseph,et al.  The Oxidation of α-Tocopherol and Trolox by Peroxynitrite , 1994 .

[15]  A. Sevanian,et al.  Linoleic acid hydroperoxide-induced peroxidation of endothelial cell phospholipids and cytotoxicity. , 1994, Free radical biology & medicine.

[16]  J. Bockaert,et al.  Glutamate receptors induce a burst of superoxide via activation of nitric oxide synthase in arginine-depleted neurons. , 1994, The Journal of biological chemistry.

[17]  Solomon H. Snyder,et al.  Janus faces of nitric oxide , 1993, Nature.

[18]  J. Bockaert,et al.  NMDA-dependent superoxide production and neurotoxicity , 1993, Nature.

[19]  B. Freeman,et al.  Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. , 1991, Archives of biochemistry and biophysics.

[20]  B. Freeman,et al.  Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. , 1991, The Journal of biological chemistry.

[21]  R. Floyd,et al.  Peroxidation induced changes in synaptosomal transport of dopamine and γ-aminobutyric acid , 1989 .

[22]  H. Rouach,et al.  Lipid peroxidation and brain mitochondrial damage induced by ethanol , 1987 .

[23]  E. Dratz,et al.  A new role for phospholipase A2: protection of membranes from lipid peroxidation damage , 1987 .

[24]  B. Ames,et al.  Detection and characterization of lipid hydroperoxides at picomole levels by high-performance liquid chromatography. , 1987, Analytical biochemistry.

[25]  R. Busto,et al.  Lipid Peroxidation In Vivo Induced by Reversible Global Ischemia in Rat Brain , 1984, Journal of neurochemistry.

[26]  T. Shima,et al.  A possible role of lipid peroxidation in cellular damages caused by cerebral ischemia and the protective effect of alpha‐tocopherol administration. , 1983, Stroke.

[27]  D. S. Fullerton,et al.  A simple method for the purification of rat brain Na+,K+-adenosine triphosphatase (ATPase). , 1982, Journal of pharmacological methods.

[28]  T. Slater,et al.  Free radicals, lipid peroxidation and cancer , 1982 .

[29]  J. Hardy,et al.  A rapid method for preparing synaptosomes: Comparison, with alternative procedures , 1981, Brain Research.

[30]  S. French,et al.  Effect of lipid hydrolysis and phosphate swelling on the structural and functional integrity of mitochondria. , 1972, Experimental and molecular pathology.

[31]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[32]  C. H. Fiske,et al.  THE COLORIMETRIC DETERMINATION OF PHOSPHORUS , 1925 .