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Reactive nitrogen species

Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH oxidase respectively. NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products, notably interferon-gamma (IFN-γ) and lipopolysaccharide (LPS).[2]

Reactions leading to generation of Nitric Oxide and Reactive Nitrogen Species. From Novo and Parola, 2008.[1]

Reactive nitrogen species act together with reactive oxygen species (ROS) to damage cells, causing nitrosative stress. Therefore, these two species are often collectively referred to as ROS/RNS.

Reactive nitrogen species are also continuously produced in plants as by-products of aerobic metabolism or in response to stress.[3]

Types edit

RNS are produced in animals starting with the reaction of nitric oxide (•NO) with superoxide (O2•−) to form peroxynitrite (ONOO):[4][5]

  • •NO (nitric oxide) + O2•− (superoxide) → ONOO (peroxynitrite)

Superoxide anion (O2) is a reactive oxygen species that reacts quickly with nitric oxide (NO) in the vasculature. The reaction produces peroxynitrite and depletes the bioactivity of NO. This is important because NO is a key mediator in many important vascular functions including regulation of smooth muscle tone and blood pressure, platelet activation, and vascular cell signaling.[6]

Peroxynitrite itself is a highly reactive species which can directly react with various biological targets and components of the cell including lipids, thiols, amino acid residues, DNA bases, and low-molecular weight antioxidants.[7] However, these reactions happen at a relatively slow rate. This slow reaction rate allows it to react more selectively throughout the cell. Peroxynitrite is able to get across cell membranes to some extent through anion channels.[8] Additionally peroxynitrite can react with other molecules to form additional types of RNS including nitrogen dioxide (•NO2) and dinitrogen trioxide (N2O3) as well as other types of chemically reactive free radicals. Important reactions involving RNS include:

  • ONOO + H+ → ONOOH (peroxynitrous acid) → •NO2 (nitrogen dioxide) + •OH (hydroxyl radical)
  • ONOO + CO2 (carbon dioxide) → ONOOCO2 (nitrosoperoxycarbonate)
  • ONOOCO2 → •NO2 (nitrogen dioxide) + O=C(O•)O (carbonate radical)
  • •NO + •NO2 ⇌ N2O3 (dinitrogen trioxide)

Biological targets edit

Peroxynitrite can react directly with proteins that contain transition metal centers. Therefore, it can modify proteins such as hemoglobin, myoglobin, and cytochrome c by oxidizing ferrous heme into its corresponding ferric forms. Peroxynitrite may also be able to change protein structure through the reaction with various amino acids in the peptide chain. The most common reaction with amino acids is cysteine oxidation. Another reaction is tyrosine nitration; however peroxynitrite does not react directly with tyrosine. Tyrosine reacts with other RNS that are produced by peroxynitrite. All of these reactions affect protein structure and function and thus have the potential to cause changes in the catalytic activity of enzymes, altered cytoskeletal organization, and impaired cell signal transduction.[8]

See also edit

References edit

  1. ^ Novo E, Parola M (2008). "Redox mechanisms in hepatic chronic wound healing and fibrogenesis". Fibrogenesis & Tissue Repair. 1 (1): 5. doi:10.1186/1755-1536-1-5. PMC 2584013. PMID 19014652.
  2. ^ Iovine NM, Pursnani S, Voldman A, Wasserman G, Blaser MJ, Weinrauch Y (March 2008). "Reactive nitrogen species contribute to innate host defense against Campylobacter jejuni". Infection and Immunity. 76 (3): 986–93. doi:10.1128/IAI.01063-07. PMC 2258852. PMID 18174337.
  3. ^ Pauly N, Pucciariello C, Mandon K, Innocenti G, Jamet A, Baudouin E, Hérouart D, Frendo P, Puppo A (2006). "Reactive oxygen and nitrogen species and glutathione: key players in the legume-Rhizobium symbiosis". Journal of Experimental Botany. 57 (8): 1769–76. doi:10.1093/jxb/erj184. PMID 16698817.
  4. ^ Squadrito GL, Pryor WA (September 1998). "Oxidative chemistry of nitric oxide: the roles of superoxide, peroxynitrite, and carbon dioxide". Free Radical Biology and Medicine. 25 (4–5): 392–403. doi:10.1016/S0891-5849(98)00095-1. PMID 9741578.
  5. ^ Dröge W (January 2002). "Free radicals in the physiological control of cell function". Physiological Reviews. 82 (1): 47–95. CiteSeerX 10.1.1.456.6690. doi:10.1152/physrev.00018.2001. PMID 11773609. S2CID 11395189.
  6. ^ Guzik TJ, West NE, Pillai R, Taggart DP, Channon KM (June 2002). "Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels". Hypertension. 39 (6): 1088–94. CiteSeerX 10.1.1.506.9055. doi:10.1161/01.HYP.0000018041.48432.B5. PMID 12052847. S2CID 2519686.
  7. ^ O'Donnell VB, Eiserich JP, Chumley PH, Jablonsky MJ, Krishna NR, Kirk M, Barnes S, Darley-Usmar VM, Freeman BA (January 1999). "Nitration of unsaturated fatty acids by nitric oxide-derived reactive nitrogen species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion". Chem. Res. Toxicol. 12 (1): 83–92. doi:10.1021/tx980207u. PMID 9894022.
  8. ^ a b Pacher P, Beckman JS, Liaudet L (January 2007). "Nitric oxide and peroxynitrite in health and disease". Physiol. Rev. 87 (1): 315–424. doi:10.1152/physrev.00029.2006. PMC 2248324. PMID 17237348.

External links edit

  • Short article on RN chemistry
  • Article on global RN trends

reactive, nitrogen, species, family, antimicrobial, molecules, derived, from, nitric, oxide, superoxide, produced, enzymatic, activity, inducible, nitric, oxide, synthase, nos2, nadph, oxidase, respectively, nos2, expressed, primarily, macrophages, after, indu. Reactive nitrogen species RNS are a family of antimicrobial molecules derived from nitric oxide NO and superoxide O2 produced via the enzymatic activity of inducible nitric oxide synthase 2 NOS2 and NADPH oxidase respectively NOS2 is expressed primarily in macrophages after induction by cytokines and microbial products notably interferon gamma IFN g and lipopolysaccharide LPS 2 Reactions leading to generation of Nitric Oxide and Reactive Nitrogen Species From Novo and Parola 2008 1 Reactive nitrogen species act together with reactive oxygen species ROS to damage cells causing nitrosative stress Therefore these two species are often collectively referred to as ROS RNS Reactive nitrogen species are also continuously produced in plants as by products of aerobic metabolism or in response to stress 3 Contents 1 Types 1 1 Biological targets 2 See also 3 References 4 External linksTypes editRNS are produced in animals starting with the reaction of nitric oxide NO with superoxide O2 to form peroxynitrite ONOO 4 5 NO nitric oxide O2 superoxide ONOO peroxynitrite Superoxide anion O2 is a reactive oxygen species that reacts quickly with nitric oxide NO in the vasculature The reaction produces peroxynitrite and depletes the bioactivity of NO This is important because NO is a key mediator in many important vascular functions including regulation of smooth muscle tone and blood pressure platelet activation and vascular cell signaling 6 Peroxynitrite itself is a highly reactive species which can directly react with various biological targets and components of the cell including lipids thiols amino acid residues DNA bases and low molecular weight antioxidants 7 However these reactions happen at a relatively slow rate This slow reaction rate allows it to react more selectively throughout the cell Peroxynitrite is able to get across cell membranes to some extent through anion channels 8 Additionally peroxynitrite can react with other molecules to form additional types of RNS including nitrogen dioxide NO2 and dinitrogen trioxide N2O3 as well as other types of chemically reactive free radicals Important reactions involving RNS include ONOO H ONOOH peroxynitrous acid NO2 nitrogen dioxide OH hydroxyl radical ONOO CO2 carbon dioxide ONOOCO2 nitrosoperoxycarbonate ONOOCO2 NO2 nitrogen dioxide O C O O carbonate radical NO NO2 N2O3 dinitrogen trioxide Biological targets edit Peroxynitrite can react directly with proteins that contain transition metal centers Therefore it can modify proteins such as hemoglobin myoglobin and cytochrome c by oxidizing ferrous heme into its corresponding ferric forms Peroxynitrite may also be able to change protein structure through the reaction with various amino acids in the peptide chain The most common reaction with amino acids is cysteine oxidation Another reaction is tyrosine nitration however peroxynitrite does not react directly with tyrosine Tyrosine reacts with other RNS that are produced by peroxynitrite All of these reactions affect protein structure and function and thus have the potential to cause changes in the catalytic activity of enzymes altered cytoskeletal organization and impaired cell signal transduction 8 See also editReactive oxygen species Reactive sulfur species Reactive carbonyl speciesReferences edit Novo E Parola M 2008 Redox mechanisms in hepatic chronic wound healing and fibrogenesis Fibrogenesis amp Tissue Repair 1 1 5 doi 10 1186 1755 1536 1 5 PMC 2584013 PMID 19014652 Iovine NM Pursnani S Voldman A Wasserman G Blaser MJ Weinrauch Y March 2008 Reactive nitrogen species contribute to innate host defense against Campylobacter jejuni Infection and Immunity 76 3 986 93 doi 10 1128 IAI 01063 07 PMC 2258852 PMID 18174337 Pauly N Pucciariello C Mandon K Innocenti G Jamet A Baudouin E Herouart D Frendo P Puppo A 2006 Reactive oxygen and nitrogen species and glutathione key players in the legume Rhizobium symbiosis Journal of Experimental Botany 57 8 1769 76 doi 10 1093 jxb erj184 PMID 16698817 Squadrito GL Pryor WA September 1998 Oxidative chemistry of nitric oxide the roles of superoxide peroxynitrite and carbon dioxide Free Radical Biology and Medicine 25 4 5 392 403 doi 10 1016 S0891 5849 98 00095 1 PMID 9741578 Droge W January 2002 Free radicals in the physiological control of cell function Physiological Reviews 82 1 47 95 CiteSeerX 10 1 1 456 6690 doi 10 1152 physrev 00018 2001 PMID 11773609 S2CID 11395189 Guzik TJ West NE Pillai R Taggart DP Channon KM June 2002 Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels Hypertension 39 6 1088 94 CiteSeerX 10 1 1 506 9055 doi 10 1161 01 HYP 0000018041 48432 B5 PMID 12052847 S2CID 2519686 O Donnell VB Eiserich JP Chumley PH Jablonsky MJ Krishna NR Kirk M Barnes S Darley Usmar VM Freeman BA January 1999 Nitration of unsaturated fatty acids by nitric oxide derived reactive nitrogen species peroxynitrite nitrous acid nitrogen dioxide and nitronium ion Chem Res Toxicol 12 1 83 92 doi 10 1021 tx980207u PMID 9894022 a b Pacher P Beckman JS Liaudet L January 2007 Nitric oxide and peroxynitrite in health and disease Physiol Rev 87 1 315 424 doi 10 1152 physrev 00029 2006 PMC 2248324 PMID 17237348 External links editShort article on RN chemistry Article on global RN trends Retrieved from https en wikipedia org w index php title Reactive nitrogen species amp oldid 1199503906, wikipedia, wiki, book, books, library,

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