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- W1986993954 abstract "There is a requirement for cellular defense against excessive peroxynitrite generation to protect against DNA strand breaks and mutations and against interference with protein tyrosine-based signaling and other protein functions due to formation of 3-nitrotyrosine. Here, we demonstrate a role of selenium-containing enzymes catalyzing peroxynitrite reduction using glutathione peroxidase (GPx) as an example. GPx protected against the oxidation of dihydrorhodamine 123 by peroxynitrite more effectively than ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoorganic compound exhibiting a high second-order rate constant for the reaction with peroxynitrite, 2 × 106m−1 s−1. Carboxymethylation of selenocysteine in GPx by iodoacetate led to the loss of “classical” glutathione peroxidase activity but maintained protection against peroxynitrite-mediated oxidation. The maintenance of protection by GPx against peroxynitrite requires GSH as reductant.When peroxynitrite was infused to maintain a 0.2 μmsteady-state concentration, GPx in the presence of GSH, but neither GPx nor GSH alone, effectively inhibited the hydroxylation of benzoate by peroxynitrite. Under these steady-state conditions peroxynitrite did not cause the loss of classical GPx activity. GPx, like selenomethionine, protected against protein 3-nitrotyrosine formation in human fibroblast lysates, shown in Western blots. The formation of nitrite rather than nitrate from peroxynitrite was enhanced by GPx or by selenomethionine. The results demonstrate a novel function of GPx and potentially of other selenoproteins containing selenocysteine or selenomethionine, in the GSH-dependent maintenance of a defense line against peroxynitrite-mediated oxidations, as a peroxynitrite reductase. There is a requirement for cellular defense against excessive peroxynitrite generation to protect against DNA strand breaks and mutations and against interference with protein tyrosine-based signaling and other protein functions due to formation of 3-nitrotyrosine. Here, we demonstrate a role of selenium-containing enzymes catalyzing peroxynitrite reduction using glutathione peroxidase (GPx) as an example. GPx protected against the oxidation of dihydrorhodamine 123 by peroxynitrite more effectively than ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a selenoorganic compound exhibiting a high second-order rate constant for the reaction with peroxynitrite, 2 × 106m−1 s−1. Carboxymethylation of selenocysteine in GPx by iodoacetate led to the loss of “classical” glutathione peroxidase activity but maintained protection against peroxynitrite-mediated oxidation. The maintenance of protection by GPx against peroxynitrite requires GSH as reductant. When peroxynitrite was infused to maintain a 0.2 μmsteady-state concentration, GPx in the presence of GSH, but neither GPx nor GSH alone, effectively inhibited the hydroxylation of benzoate by peroxynitrite. Under these steady-state conditions peroxynitrite did not cause the loss of classical GPx activity. GPx, like selenomethionine, protected against protein 3-nitrotyrosine formation in human fibroblast lysates, shown in Western blots. The formation of nitrite rather than nitrate from peroxynitrite was enhanced by GPx or by selenomethionine. The results demonstrate a novel function of GPx and potentially of other selenoproteins containing selenocysteine or selenomethionine, in the GSH-dependent maintenance of a defense line against peroxynitrite-mediated oxidations, as a peroxynitrite reductase. Peroxynitrite is a potent biological oxidant (1Beckman J.S. Beckman T.W. Chen J. Marshall P. Freeman B.A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 1620-1624Crossref PubMed Scopus (6666) Google Scholar) generated,e.g. by endothelial cells, Kupffer cells, neutrophils, and macrophages (see Beckman (2Beckman J.S. Lancaster J. Nitric Oxide. Principles and Actions. Academic Press, San Diego, CA1996: 1-82Google Scholar) for review). Peroxynitrite (ONOO−) is a relatively stable species compared with free radicals, but peroxynitrous acid (ONOOH) decays with a rate constant of 1.3 s−1. Peroxynitrite is a mediator of toxicity in inflammatory processes with strong oxidizing properties toward biological molecules, including sulfhydryls, ascorbate, lipids, amino acids, and nucleotides, and it can cause strand breaks in DNA. Free or protein-bound tyrosine residues and other phenolics can be nitrated by peroxynitrite (see Beckman (2Beckman J.S. Lancaster J. Nitric Oxide. Principles and Actions. Academic Press, San Diego, CA1996: 1-82Google Scholar) for review). Protein tyrosine nitration may interfere with phosphorylation/dephosphorylation signaling (3Kong S.-K. Yim M.B. Stadtman E. Chock P.B. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3377-3382Crossref PubMed Scopus (308) Google Scholar), and the in vivo occurrence of protein nitration in the human has been demonstrated in patients chronically rejecting renal allografts (4MacMillan-Crow L.A. Crow J.P. Kerby J.D. Beckman J.S. Thompson J.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 11853-11858Crossref PubMed Scopus (716) Google Scholar). 3-Nitrotyrosine plasma levels of up to 0.12 mm were observed in chronic renal failure patients with septic shock (5Fukuyama N. Takebayashi Y. Hida M. Ishida H. Ichimori K. Nakazawa H. Free Radical Biol. Med. 1997; 22: 771-774Crossref PubMed Scopus (164) Google Scholar).The selenium-containing compound, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) (6Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 262-267Crossref PubMed Scopus (153) Google Scholar) and its main metabolite in vivo, 2-(methylseleno)benzanilide (7Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 1057-1062Crossref PubMed Scopus (29) Google Scholar), react with peroxynitrite very efficiently. Ebselen, selenocysteine, and selenomethionine protected DNA from single-strand break formation caused by peroxynitrite more effectively than their sulfur-containing analogs (8Roussyn I. Briviba K. Masumoto H. Sies H. Arch. Biochem. Biophys. 1996; 330: 216-218Crossref PubMed Scopus (107) Google Scholar). Furthermore, these selenocompounds were protective in model oxidation and nitration reactions mediated by peroxynitrite (9Briviba K. Roussyn I. Sharov V. Sies H. Biochem. J. 1996; 319: 13-15Crossref PubMed Scopus (114) Google Scholar).Ebselen is known as a mimic of the GSH peroxidase (GPx) 1The abbreviations used are: GPx, glutathione peroxidase; DTPA, diethylenetriamine pentaacetic acid; BSA, bovine serum albumin. 1The abbreviations used are: GPx, glutathione peroxidase; DTPA, diethylenetriamine pentaacetic acid; BSA, bovine serum albumin. reaction (10Müller A. Cadenas E. Graf P. Sies H. Biochem. Pharmacol. 1984; 33: 3235-3239Crossref PubMed Scopus (734) Google Scholar). We hypothesized (11Sies H. Masumoto H. Adv. Pharmacol. 1997; 38: 229-246Crossref PubMed Scopus (214) Google Scholar) that its newly found reactivity with peroxynitrite (6Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 262-267Crossref PubMed Scopus (153) Google Scholar) mimics a so far undescribed peroxynitrite reductase activity of selenoproteins. The present work provides evidence for a protective function of GPx against peroxynitrite. Peroxynitrite is a potent biological oxidant (1Beckman J.S. Beckman T.W. Chen J. Marshall P. Freeman B.A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 1620-1624Crossref PubMed Scopus (6666) Google Scholar) generated,e.g. by endothelial cells, Kupffer cells, neutrophils, and macrophages (see Beckman (2Beckman J.S. Lancaster J. Nitric Oxide. Principles and Actions. Academic Press, San Diego, CA1996: 1-82Google Scholar) for review). Peroxynitrite (ONOO−) is a relatively stable species compared with free radicals, but peroxynitrous acid (ONOOH) decays with a rate constant of 1.3 s−1. Peroxynitrite is a mediator of toxicity in inflammatory processes with strong oxidizing properties toward biological molecules, including sulfhydryls, ascorbate, lipids, amino acids, and nucleotides, and it can cause strand breaks in DNA. Free or protein-bound tyrosine residues and other phenolics can be nitrated by peroxynitrite (see Beckman (2Beckman J.S. Lancaster J. Nitric Oxide. Principles and Actions. Academic Press, San Diego, CA1996: 1-82Google Scholar) for review). Protein tyrosine nitration may interfere with phosphorylation/dephosphorylation signaling (3Kong S.-K. Yim M.B. Stadtman E. Chock P.B. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 3377-3382Crossref PubMed Scopus (308) Google Scholar), and the in vivo occurrence of protein nitration in the human has been demonstrated in patients chronically rejecting renal allografts (4MacMillan-Crow L.A. Crow J.P. Kerby J.D. Beckman J.S. Thompson J.A. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 11853-11858Crossref PubMed Scopus (716) Google Scholar). 3-Nitrotyrosine plasma levels of up to 0.12 mm were observed in chronic renal failure patients with septic shock (5Fukuyama N. Takebayashi Y. Hida M. Ishida H. Ichimori K. Nakazawa H. Free Radical Biol. Med. 1997; 22: 771-774Crossref PubMed Scopus (164) Google Scholar). The selenium-containing compound, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) (6Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 262-267Crossref PubMed Scopus (153) Google Scholar) and its main metabolite in vivo, 2-(methylseleno)benzanilide (7Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 1057-1062Crossref PubMed Scopus (29) Google Scholar), react with peroxynitrite very efficiently. Ebselen, selenocysteine, and selenomethionine protected DNA from single-strand break formation caused by peroxynitrite more effectively than their sulfur-containing analogs (8Roussyn I. Briviba K. Masumoto H. Sies H. Arch. Biochem. Biophys. 1996; 330: 216-218Crossref PubMed Scopus (107) Google Scholar). Furthermore, these selenocompounds were protective in model oxidation and nitration reactions mediated by peroxynitrite (9Briviba K. Roussyn I. Sharov V. Sies H. Biochem. J. 1996; 319: 13-15Crossref PubMed Scopus (114) Google Scholar). Ebselen is known as a mimic of the GSH peroxidase (GPx) 1The abbreviations used are: GPx, glutathione peroxidase; DTPA, diethylenetriamine pentaacetic acid; BSA, bovine serum albumin. 1The abbreviations used are: GPx, glutathione peroxidase; DTPA, diethylenetriamine pentaacetic acid; BSA, bovine serum albumin. reaction (10Müller A. Cadenas E. Graf P. Sies H. Biochem. Pharmacol. 1984; 33: 3235-3239Crossref PubMed Scopus (734) Google Scholar). We hypothesized (11Sies H. Masumoto H. Adv. Pharmacol. 1997; 38: 229-246Crossref PubMed Scopus (214) Google Scholar) that its newly found reactivity with peroxynitrite (6Masumoto H. Sies H. Chem. Res. Toxicol. 1996; 9: 262-267Crossref PubMed Scopus (153) Google Scholar) mimics a so far undescribed peroxynitrite reductase activity of selenoproteins. The present work provides evidence for a protective function of GPx against peroxynitrite. We thank Dr. N. Kashirina for help with the nitrite analyses." @default.
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- W1986993954 title "Glutathione Peroxidase Protects against Peroxynitrite-mediated Oxidations" @default.
- W1986993954 cites W1500094754 @default.
- W1986993954 cites W1560877971 @default.
- W1986993954 cites W1589162257 @default.
- W1986993954 cites W1761291408 @default.
- W1986993954 cites W1805258373 @default.
- W1986993954 cites W1969553244 @default.
- W1986993954 cites W1972438028 @default.
- W1986993954 cites W1983102597 @default.
- W1986993954 cites W1986669241 @default.
- W1986993954 cites W1987861061 @default.
- W1986993954 cites W1999010068 @default.
- W1986993954 cites W1999649376 @default.
- W1986993954 cites W2003425269 @default.
- W1986993954 cites W2009176903 @default.
- W1986993954 cites W2021914341 @default.
- W1986993954 cites W2022345730 @default.
- W1986993954 cites W2028575675 @default.
- W1986993954 cites W2029040572 @default.
- W1986993954 cites W2034722849 @default.
- W1986993954 cites W2039626545 @default.
- W1986993954 cites W2046798893 @default.
- W1986993954 cites W2051899684 @default.
- W1986993954 cites W2058013605 @default.
- W1986993954 cites W2058137293 @default.
- W1986993954 cites W2060292403 @default.
- W1986993954 cites W2064437259 @default.
- W1986993954 cites W2067753981 @default.
- W1986993954 cites W2068576735 @default.
- W1986993954 cites W2071321282 @default.
- W1986993954 cites W2090316954 @default.
- W1986993954 cites W2092721077 @default.
- W1986993954 cites W2126865336 @default.
- W1986993954 cites W2331629748 @default.
- W1986993954 cites W2343482706 @default.
- W1986993954 cites W312187524 @default.
- W1986993954 cites W4251440173 @default.
- W1986993954 cites W995921749 @default.
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