... Since several groups have reported the value of the extinction coefficient at 660 15 DP Barr ... more ... Since several groups have reported the value of the extinction coefficient at 660 15 DP Barr and SD Aust, Arch. Biochem. Biophys. 303, 377 (1993). ... Chem. Res. Toxicol., 7 (1994), p. 628. 15 DP Barr and SD Aust. Arch. Biochem. Biophys., 303 (1993), p. 377. ...
Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells... more Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H202). Murine neutrophils and activated macrophages, however, produce NO, H202, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coh~ with NO and H202 for 30 rain and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H202-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O 2 induced DNA double strand breaks in the bacterial gehome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H202 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H202 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H202-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO.
4 Groupe 'Radiochimie de l&a... more 4 Groupe 'Radiochimie de l'ADN', U347 INSERM, 80, rue du General Lectere 94276, LE. Kremilin Bicetre Cedex, Villejuif, Cedex, France. ... 5 Groupe Reparation des lesions radio et chimio-induites'URA 147 CRNS Institut Gustave-Roussy PR II, 94805 Villejuif, Cedex, ...
NO do not protect. Similar results were observed for NO donors studied when hypoxanthine/xanthine... more NO do not protect. Similar results were observed for NO donors studied when hypoxanthine/xanthine oxi-The role that nitric oxide (NO) plays in various dedase was used as the source for ROS, although the Sgenerative and disease states has remained a mysnitrosothiol agents were much less protective. These tery since its discovery as a biological messenger, results demonstrate that NO possesses properties prompting the question, ''NO, friend or foe?'' Some which protect against ROS toxicity and demonstrate reports have suggested that NO is cytotoxic, and yet how the use of different NO donor compounds can others have shown that it possesses protective proplead to different conclusions about the role that NO erties against reactive oxygen species (ROS). Many can play in the cytotoxicity of ROS. ᭧ 1996 Academic Press, studies have used various NO donor complexes arriv-Inc.
Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic ox... more Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H2O2, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.
... Since several groups have reported the value of the extinction coefficient at 660 15 DP Barr ... more ... Since several groups have reported the value of the extinction coefficient at 660 15 DP Barr and SD Aust, Arch. Biochem. Biophys. 303, 377 (1993). ... Chem. Res. Toxicol., 7 (1994), p. 628. 15 DP Barr and SD Aust. Arch. Biochem. Biophys., 303 (1993), p. 377. ...
Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells... more Previously, we reported that nitric oxide (NO) provides significant protection to mammalian cells from the cytotoxic effects of hydrogen peroxide (H202). Murine neutrophils and activated macrophages, however, produce NO, H202, and other reactive oxygen species to kill microorganisms, which suggests a paradox. In this study, we treated bacteria (Escherichia coh~ with NO and H202 for 30 rain and found that exposure to NO resulted in minimal toxicity, but greatly potentiated (up to 1,000-fold) H202-mediated killing, as evaluated by a clonogenic assay. The combination of NO/H2O 2 induced DNA double strand breaks in the bacterial gehome, as shown by field-inverted gel electrophoresis, and this increased DNA damage may correlate with cell killing. NO was also shown to alter cellular respiration and decrease the concentration of the antioxidant glutathione to a residual level of 15-20% in bacterial cells. The iron chelator desferrioxamine did not stop the action of NO on respiration and glutathione decrease, yet it prevented the NO/H202 synergistic cytotoxicity, implicating metal ions as critical participants in the NO/H202 cytocidal mechanism. Our results suggest a possible mechanism of modulation of H202-mediated toxicity, and we propose a new key role in the antimicrobial macrophagic response for NO.
4 Groupe 'Radiochimie de l&a... more 4 Groupe 'Radiochimie de l'ADN', U347 INSERM, 80, rue du General Lectere 94276, LE. Kremilin Bicetre Cedex, Villejuif, Cedex, France. ... 5 Groupe Reparation des lesions radio et chimio-induites'URA 147 CRNS Institut Gustave-Roussy PR II, 94805 Villejuif, Cedex, ...
NO do not protect. Similar results were observed for NO donors studied when hypoxanthine/xanthine... more NO do not protect. Similar results were observed for NO donors studied when hypoxanthine/xanthine oxi-The role that nitric oxide (NO) plays in various dedase was used as the source for ROS, although the Sgenerative and disease states has remained a mysnitrosothiol agents were much less protective. These tery since its discovery as a biological messenger, results demonstrate that NO possesses properties prompting the question, ''NO, friend or foe?'' Some which protect against ROS toxicity and demonstrate reports have suggested that NO is cytotoxic, and yet how the use of different NO donor compounds can others have shown that it possesses protective proplead to different conclusions about the role that NO erties against reactive oxygen species (ROS). Many can play in the cytotoxicity of ROS. ᭧ 1996 Academic Press, studies have used various NO donor complexes arriv-Inc.
Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic ox... more Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (O2.-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with O2.- ranging from 1.1 x 10(3) to 1.3 x 10(6) M-1 s-1. These SOD mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H2O2, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-FeII and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies.
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