DOCSLIB.ORG

A New Gaseous Signaling Molecule Emerges: Cardioprotective Role of Hydrogen Sulfide

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A New Gaseous Signaling Molecule Emerges: Cardioprotective Role of Hydrogen Sulfide COMMENTARY A new gaseous signaling molecule emerges: Cardioprotective role of hydrogen sulfide David J. Lefer* Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461 ardiovascular (CV) research has largely been focused on two endogenously produced gaseous signaling molecules, Cnamely, nitric oxide (NO) and carbon monoxide (CO). These gaseous messen- gers are both highly conserved evolu- tionarily and synthesized by endogenous enzyme systems. Extensive research ef- forts have uniformly demonstrated that CO- and NO-based therapeutics protect the brain, heart, and circulation against a number of CV disease states (1–3). However, controversy exists regarding the therapeutic value of both CO and NO, with some studies citing NO cyto- toxicity at very high levels and under certain conditions (2). The toxic effects of NO are related to the highly reactive nature of NO and its interaction with superoxide to form the potent oxidant peroxynitrite (ONOOϪ) (2). Very re- cently, a third endogenously produced gaseous signaling molecule, hydrogen sulfide (H2S), has emerged as a poten- tially important mediator of CV homeo- stasis and cytoprotection (3). In this Fig. 1. Summary of the physiological actions of hydrogen sulfide (H2S). H2S is produced in micromolar issue of PNAS, Benavides et al. (4) re- (i.e., 10–100 ␮M) concentrations in the circulation and exerts a number of critical effects on the CV system. veal that the vasculoprotective and anti- H2S has been shown to induce vasodilation and inhibit leukocyte-endothelial cell interactions in the circulation. H2S is a potent antioxidant and inhibits cellular apoptosis. H2S also has been shown to hypertensive effects of dietary garlic transiently and reversibly inhibit mitochondrial respiration. Taken together, this physiological profile is (Allium sativum) are mediated in large ideally suited for protection of the CV system against disease states. part via the generation of H2S. Previous studies indicate that dietary garlic consumption is inversely corre- leads to vasorelaxation via vascular wise, thiocysteine generated by CGL can lated with the progression and severity smooth muscle KATP channel-mediated interact with thiols to generate H2S(6– of CV disease and that it affects a lower hyperpolarization (3). These novel ex- 8). The endogenous production of H2S incidence of hypertension (5). However, perimental studies provide important was initially described in the brain and the mechanism(s) by which consumption information regarding the mechanisms attributed to CBS (7–9). In addition, of garlic attenuates CV disease has in responsible for garlic-mediated attenua- H2S is produced in the vasculature by large part remained a mystery. Benav- tion of hypertension and serve to high- CGL, where it mediates smooth muscle ides et al. (4) elegantly demonstrate that light the potential importance of H2S relaxation and subsequent vasodilation garlic-derived organic polysulfides are therapy in CV disease. (3). At present, the distribution of CGL converted by red blood cells (RBCs) H2S is well known as a toxic gas with and CBS throughout the body are not into hydrogen sulfide gas. Interestingly, a repulsive odor often used to describe well characterized. Furthermore, very the garlic bulbs used for this study were the smell of rotten eggs (3). Experimen- little is currently known regarding the obtained from local supermarkets in the tal studies reveal that H2S is produced functions of CBS and CGL under physi- city of Birmingham, AL, and then enzymatically at micromolar levels in ological and pathophysiological condi- pressed by the investigators to obtain mammals and exerts a number of physi- tions. As this rapidly emerging field garlic juice on the day of the experiment. ological actions in the CV system (3, 6, advances, we are likely to learn a great The bioconversion of polysulfides to 7). H2S production has been attributed H2S is enhanced by glucose-maintained to two key enzymes in the cysteine bio- Author contributions: D.J.L. wrote the paper. cytosolic glutathione levels and depends synthesis pathway, cystathionine ␤- Conflict of interest statement: The author is currently on reduced thiols in close proximity to synthase (CBS) and cystathionine funded by Ikaria Corporation for a research grant and the RBC membrane. The authors dem- ␥-lyase (CGL). CBS and CGL are both serves as a paid Consultant for Ikaria Corporation. Ikaria is onstrate that generation of H2S after heme-containing enzymes whose activity currently developing hydrogen sulfide therapy for a num- bioconversion of garlic-derived polysul- depends on the cofactor pyridoxal 5Ј- ber of disease states. fides results in potent vasorelaxation of phosphate (6–8). CBS is capable of cat- See the companion article on page 17977. isolated blood vessels. The authors pro- alyzing the reaction of cysteine with *E-mail: [email protected]. pose that H2S produced from garlic other free thiols to generate H2S; like- © 2007 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0709010104 PNAS ͉ November 13, 2007 ͉ vol. 104 ͉ no. 46 ͉ 17907–17908 Downloaded by guest on September 30, 2021 deal regarding the biochemistry and during myocardial ischemia and reperfu- left ventricular (LV) function in a clini- physiology of these H2S-producing en- sion (I/R) (10). The mitochondrial ef- cally relevant, in vivo model of acute zyme systems. fects of H2S have been shown to be myocardial infarction. Furthermore, car- Since the recent discovery that H2Sis mediated in part by reversible and po- diac-specific overexpression of the H2S- a powerful gaseous signaling molecule, tent inhibition of cytochrome c oxidase generating enzyme CGL significantly studies have begun to characterize the (complex IV of the mitochondrial elec- reduces myocardial I/R injury and simi- biological profile of this promiscuous tron transport chain) (10, 13). The de- larly preserves LV function (10). The gas. Fig. 1 summarizes some of the fined physiological profile of H2S makes authors propose that preservation of physiological actions of H2S in the CV cardiac mitochondrial structure and system. H2S has been shown to relax function is central in the cardioprotec- vascular smooth muscle, induce vaso- It appears that H2S tive actions of H2S in I/R injury. dilation of isolated blood vessels, and Recent investigations into the vascular reduce blood pressure (3, 10). In this possesses all of the effects of H2S have revealed that this regard, H2S might be an important regula- physiologically produced gas has pro- tor of blood pressure. H2S has also been positive effects of NO found effects on vascular growth or for- shown to inhibit leukocyte–endothelial mation and neointimal hyperplasia. cell interactions in vivo. Zanardo et al. without the capacity to Meng et al. (18) have very recently (11) used intravital microscopy to dem- demonstrated that H2S ameliorates the onstrate that H2S donors inhibit leuko- form a toxic metabolite. intimal hyperplasia response in blood cyte adherence in the rat mesenteric vessels after balloon-mediated vascular microcirculation during vascular inflam- injury. Furthermore, Cai et al. (19) have mation, suggesting that H2S is a potent this novel gaseous signaling molecule an reported that physiologically relevant antiinflammatory molecule. It has also ideal pharmacological candidate for the dosages of H2S promote a highly robust become evident that H2S is as a potent treatment of CV disease states. angiogenic response that is largely de- antioxidant and, under chronic condi- A number of recent studies have pro- pendent on activation of Akt. Thus, H2S tions, can up-regulate antioxidant de- vided insights into the protective actions may prove beneficial for the inhibition fenses (9). In addition, it has been of H2S in the setting of myocardial I/R of coronary artery restenosis and the demonstrated that H2S effectively inhib- injury (10, 14–17). Pretreatment with induction of therapeutic angiogenesis. its apoptosis of a number of cell types, the H2S donor (NaHS) reduces arrhyth- Clearly, additional research is war- and this effect has been shown to pro- mias in isolated hearts subjected to ranted to further our understanding of mote cytoprotection (9). global cardiac I/R and improves myocyte the synthesis, metabolism, and physio- Research interest in H2S has also survival (14, 15). Similarly, Johansen et logical and potentially pathophysiologi- been focused on its profound metabolic al. (16) reported that NaHS pretreat- cal actions of endogenously produced effects, which result in a state of sus- ment significantly attenuates myocardial H2S in mammalian systems. The biologi- pended animation with drastic reduction injury in isolated, perfused rat hearts cal profile of H2S strongly suggests that in metabolic demand (12). Initiating sus- subjected to cardiac I/R. An article by this gaseous signaling molecule is likely pended animation may prove to be an Sivarajah et al. (17) represents the first to protect a variety of organs despite its ideal therapy for various shock or report of the cardioprotective actions of prior reputation as a noxious gas with a trauma states in which dramatic reduc- H2Sinanin vivo model of myocardial repulsive odor. It appears that H2S pos- tions in metabolic demands may be I/R injury. The authors reported a 25% sesses all of the positive effects of NO highly protective. Studies investigating reduction in myocardial infarct size after without the
Load more

Recommended publications
  • Oxygen Is Instrumental for Biological Signaling: an Overview
    Review Oxygen Is Instrumental for Biological Signaling: An Overview John T. Hancock Department of Applied Sciences, University of the West of England, Bristol BS16 1QY, UK; [email protected]; Tel.: +44-(0)117-328-2475 Abstract: Control of cellular function is extremely complex, being reliant on a wide range of compo- nents. Several of these are small oxygen-based molecules. Although reactive compounds containing oxygen are usually harmful to cells when accumulated to relatively high concentrations, they are also instrumental in the control of the activity of a myriad of proteins, and control both the upregulation and downregulation of gene expression. The formation of one oxygen-based molecule, such as the superoxide anion, can lead to a cascade of downstream generation of others, such as hydrogen · peroxide (H2O2) and the hydroxyl radical ( OH), each with their own reactivity and effect. Nitrogen- based signaling molecules also contain oxygen, and include nitric oxide (NO) and peroxynitrite, both instrumental among the suite of cell signaling components. These molecules do not act alone, but form part of a complex interplay of reactions, including with several sulfur-based compounds, such as glutathione and hydrogen sulfide (H2S). Overaccumulation of oxygen-based reactive compounds may alter the redox status of the cell and lead to programmed cell death, in processes referred to as oxidative stress, or nitrosative stress (for nitrogen-based molecules). Here, an overview of the main oxygen-based molecules involved, and the ramifications of their production, is given. Keywords: carbon monoxide; hydrogen peroxide; hydroxyl radicals; hydrogen sulfide; NADPH oxidase; nitric oxide; peroxynitrite; redox; superoxide Citation: Hancock, J.T.
    [Show full text]
  • Hydrogen Sulfide Metabolite, Sodium Thiosulfate
    International Journal of Molecular Sciences Review Hydrogen Sulfide Metabolite, Sodium Thiosulfate: Clinical Applications and Underlying Molecular Mechanisms Max Y. Zhang 1,2, George J. Dugbartey 1,2,3, Smriti Juriasingani 1,3 and Alp Sener 1,2,3,4,* 1 Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, ON N6A 5A5, Canada; [email protected] (M.Y.Z.); [email protected] (G.J.D.); [email protected] (S.J.) 2 London Health Sciences Center, Multi-Organ Transplant Program, Western University, London, ON N6A 5A5, Canada 3 London Health Sciences Center, Department of Surgery, Division of Urology, Western University, London, ON N6A 5A5, Canada 4 Department of Microbiology & Immunology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada * Correspondence: [email protected]; Tel.: +1(519) 6633352 Abstract: Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (H2S), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review Citation: Zhang, M.Y.; Dugbartey, discusses the biochemical and molecular pathways in the generation of STS from H2S, its clinical G.J.; Juriasingani, S.; Sener, A. usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these Hydrogen Sulfide Metabolite, clinical applications and a future perspective in kidney transplantation.
    [Show full text]
  • Mitochondrial Peroxynitrite Generation Is Mainly Driven by Superoxide Steady-State Concentration Rather Than by Nitric Oxide Steady-State Concentration
    International Journal of Molecular Biology: Open Access Review Article Open Access Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration Abstract Volume 3 Issue 2 - 2018 - - In biological systems, ONOO production depends on production rates of NO and O2 , and on the reactions of these two free radicals with other biological components, which Laura B Valdez,1,2 Silvina S Bombicino,1 Darío limit the local concentrations of NO and O -. In mitochondria, O - is generated through 2 2 E Iglesias,1,2 Ivana Rukavina Mikusic A,1,2 the auto oxidation of semiquinones at Complexes I and III, and it may suffer the SOD- 1,2 catalyzed dismutation reaction to produce H O or react with NO in a classical termination Alberto Boveris 2 2 1 reaction between free radicals. These diffusion-controlled reactions kinetically compete for University of Buenos Aires, Physical Chemistry Division, Argentina O - degradation. Results from our laboratory have shown that even in physiopathological 2 2 situations in which NO production is reduced, such as the mitochondrial dysfunction University of Buenos Aires, Institute of Biochemistry and Molecular Medicine (IBIMOL), Argentina associated to stunned heart, mitochondrial ONOO- production rate may be slightly - - increased if the steady-state concentration of O2 is augmented. The enhancement in O2 concentration leads to an increase in its degradation by reaction with NO, decreasing NO Correspondence: Laura B Valdez, Cátedra de Fisicoquímica, bioavailability and increasing ONOO- production rate. Therefore, mitochondrial ONOO- Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina, Tel+ 54-11-5287- generation is mainly driven by O - rather than by NO steady-state concentrations.
    [Show full text]
  • On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas
    biomolecules Article On the Liquid Chemistry of the Reactive Nitrogen Species Peroxynitrite and Nitrogen Dioxide Generated by Physical Plasmas Giuliana Bruno 1, Sebastian Wenske 1, Jan-Wilm Lackmann 2, Michael Lalk 3 , Thomas von Woedtke 4 and Kristian Wende 1,* 1 Centre for Innovation Competence (ZIK) Plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany; [email protected] (G.B.); [email protected] (S.W.) 2 Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany; [email protected] 3 Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany; [email protected] 4 Leibniz Institute for Plasma Science and Technology, 17489 Greifswald, Germany; [email protected] * Correspondence: [email protected] Received: 9 November 2020; Accepted: 9 December 2020; Published: 16 December 2020 Abstract: Cold physical plasmas modulate cellular redox signaling processes, leading to the evolution of a number of clinical applications in recent years. They are a source of small reactive species, including reactive nitrogen species (RNS). Wound healing is a major application and, as its physiology involves RNS signaling, a correlation between clinical effectiveness and the activity of plasma-derived RNS seems evident. To investigate the type and reactivity of plasma-derived RNS in aqueous systems, a model with tyrosine as a tracer was utilized. By high-resolution mass spectrometry, 26 different tyrosine derivatives including the physiologic nitrotyrosine were identified. The product pattern was distinctive in terms of plasma parameters, especially gas phase composition. By scavenger experiments and isotopic labelling, gaseous nitric dioxide radicals and liquid phase peroxynitrite ions were determined as dominant RNS.
    [Show full text]
  • Inhibition of Mitochondrial Respiratory Complex I by Nitric Oxide, Peroxynitrite and S-Nitrosothiols
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1658 (2004) 44–49 www.bba-direct.com Review Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols Guy C. Brown*, Vilmante Borutaite Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK Received 18 February 2004; accepted 4 March 2004 Available online 15 June 2004 Abstract NO or its derivatives (reactive nitrogen species, RNS) inhibit mitochondrial complex I by several different mechanisms that are not well characterised. There is an inactivation by NO, peroxynitrite and S-nitrosothiols that is reversible by light or reduced thiols, and therefore may be due to S-nitrosation or Fe-nitrosylation of the complex. There is also an irreversible inhibition by peroxynitrite, other oxidants and high levels of NO, which may be due to tyrosine nitration, oxidation of residues or damage of iron sulfur centres. Inactivation of complex I by NO or RNS is seen in cells or tissues expressing iNOS, and may be relevant to inflammatory pathologies, such as septic shock and Parkinson’s disease. D 2004 Elsevier B.V. All rights reserved. Keywords: Nitric oxide; Mitochondria; Complex I; NADH-ubiquinone oxidoreductase; Parkinson’s disease; Respiration 1. Complex I subunit of complex I has been identified as an acyl carrier protein [3] and might be involved in biosynthesis of lipoic Mitochondrial respiratory complex I (NADH:ubiquinone acid. There are also three possible links between complex I oxidoreductase) is a large and complex enzyme coupling functions and cell death.
    [Show full text]
  • The Decomposition of Peroxynitrite to Nitroxyl Anion (NO ) and Singlet
    The decomposition of peroxynitrite to nitroxyl anion NO؊) and singlet oxygen in aqueous solution) Ahsan Ullah Khan*†, Dianne Kovacic*, Alexander Kolbanovskiy*, Mehul Desai‡, Krystyna Frenkel‡, and Nicholas E. Geacintov* *Department of Chemistry, New York University, New York, NY 10003; and †Department of Environmental Medicine, New York University, New York, NY 10016 Communicated by Michael Kasha, Florida State University, Tallahassee, FL, December 31, 1999 (received for review November 22, 1999) The mechanism of decomposition of peroxynitrite (OONO؊)in reaction of the acidic with the basic reactant and the local aqueous sodium phosphate buffer solution at neutral pH was non-equilibrium conditions made extrapolating this interpreta- investigated. The OONO؊ was synthesized by directly reacting tion to biological conditions at pH 7 uncertain. We decided to nitric oxide with superoxide anion at pH 13. The hypothesis was examine the nature of the reactive species generated in the explored that OONO؊, after protonation at pH 7.0 to HOONO, decomposition of peroxynitrite under more controlled and 1 decomposes into O2 and HNO according to a spin-conserved physiologically relevant conditions. unimolecular mechanism. Small aliquots of the concentrated alka- In this communication we report an important reaction path- line OONO؊ solution were added to a buffer solution (final pH way for the decomposition of peroxynitrite that yields two ؊ Ϫ 1 7.0–7.2), and the formation of O2 and NO in high yields was transient species, nitroxyl anion (NO ) and singlet molecular 1 observed. The O2 generated was trapped as the transannular oxygen. By using well established analytical procedures, an Ϸ peroxide (DPAO2) of 9,10-diphenylanthracene (DPA) dissolved in aqueous alkaline solution (pH 13) of peroxynitrite was allowed carbon tetrachloride.
    [Show full text]
  • Tetrahydrobiopterin and the Regulation of Hypoxic Pulmonary Vasoconstriction
    Eur Respir J 2010; 36: 323–330 DOI: 10.1183/09031936.00188809 CopyrightßERS 2010 Tetrahydrobiopterin and the regulation of hypoxic pulmonary vasoconstriction B.N. Francis, M.R. Wilkins and L. Zhao ABSTRACT: Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS). AFFILIATIONS Experimental Medicine and This study investigated the effect of increasing BH4 levels on hypoxia-induced pulmonary Toxicology, Imperial College London, vasoconstriction (HPV). Hammersmith Hospital, London, UK. Sprague Dawley rats and hph-1 (BH4 deficient) mice were given BH4 before and during HPV in an isolated perfused lung preparation. BH4 inhibited HPV in a concentration-dependent manner CORRESPONDENCE and increased NO metabolites in the perfusate. Bradykinin-induced reductions in HPV were L. Zhao Experimental Medicine and blunted in hph-1 mice and pre-administration of BH4 restored the response. The effect of BH4 was Toxicology, Imperial College London attenuated by L-NAME (NOS inhibitor), PTIO (NO scavenger), and catalase (H2O2 catalyser) Hammersmith Hospital administered prior to HPV but enhanced by MnTMPyP (superoxide dismutase mimetic). The effect Ducane Road London of BH4 on HPV was partially recapitulated by NH4, a stereoisomer that shares antioxidant W12 ONN properties with BH4 but is not a NOS cofactor. UK The bioavailability of BH4 is an important determinant of the pulmonary vascular response to E-mail: [email protected] hypoxia. Its effects are mediated via nitric oxide, hydrogen peroxide and its antioxidant properties,
    [Show full text]
  • Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No
    Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5) Volume II JACC No. 53 ISSN-0773-6339-53 Brussels, September 2007 Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5) ECETOC JACC REPORT No. 53 © Copyright – ECETOC AISBL European Centre for Ecotoxicology and Toxicology of Chemicals 4 Avenue E. Van Nieuwenhuyse (Bte 6), B-1160 Brussels, Belgium. All rights reserved. No part of this publication may be reproduced, copied, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the copyright holder. Applications to reproduce, store, copy or translate should be made to the Secretary General. ECETOC welcomes such applications. Reference to the document, its title and summary may be copied or abstracted in data retrieval systems without subsequent reference. The content of this document has been prepared and reviewed by experts on behalf of ECETOC with all possible care and from the available scientific information. It is provided for information only. ECETOC cannot accept any responsibility or liability and does not provide a warranty for any use or interpretation of the material contained in the publication. ECETOC JACC No. 53 Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5) Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin CONTENTS - VOLUMES I AND II EXECUTIVE SUMMARY 1 THE ECETOC SCHEME FOR THE JOINT ASSESSMENT OF COMMODITY CHEMICALS 3 1.
    [Show full text]
  • Widespread Peroxynitrite-Mediated Damage in Alzheimer's Disease
    The Journal of Neuroscience, April 15, 1997, 17(8):2653–2657 Widespread Peroxynitrite-Mediated Damage in Alzheimer’s Disease Mark A. Smith,1 Peggy L. Richey Harris,1 Lawrence M. Sayre,2 Joseph S. Beckman,3 and George Perry1 1Institute of Pathology and 2Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, and 3Department of Anesthesiology, School of Medicine, University of Alabama, Birmingham, Alabama 35233 Increasing evidence suggests that oxidative damage to pro- indicator of peroxynitrite involvement. In brain tissue from teins and other macromolecules is a salient feature of the cases of Alzheimer’s disease, we found increased protein ni- pathology of Alzheimer’s disease. Establishing the source of tration in neurons, including but certainly not restricted to those oxidants is key to understanding what role they play in the containing neurofibrillary tangles (NFTs). Conversely, nitroty- pathogenesis of Alzheimer’s disease, and one way to examine rosine was undetectable in the cerebral cortex of age-matched this issue is to determine which oxidants are involved in control brains. This distribution is essentially identical to that of damage. free carbonyls. In this study, we examine whether peroxynitrite, a powerful These findings provide strong evidence that peroxynitrite is oxidant produced from the reaction of superoxide with nitric involved in oxidative damage of Alzheimer’s disease. Moreover, oxide, is involved in Alzheimer’s disease. Peroxynitrite is a the widespread occurrence of nitrotyrosine in neurons sug- source of hydroxyl radical-like reactivity, and it directly oxidizes gests that oxidative damage is not restricted to long-lived proteins and other macromolecules with resultant carbonyl polymers such as NFTs, but instead reflects a generalized formation from side-chain and peptide-bond cleavage.
    [Show full text]
  • Measurements of Nitric Oxide and Peroxynitrite Hideharu Shintani* Chuo University, School of Science, 1-13-27, Kasuga Bunkyo 112-0003 Tokyo, Japan
    A tica nal eu yt c ic a a m A r a c t Shintani, Pharm Anal Acta 2013, 4:6 h a P DOI: 10.4172/2153-2435.1000251 ISSN: 2153-2435 Pharmaceutica Analytica Acta Short Communication Open Access Measurements of Nitric Oxide and Peroxynitrite Hideharu Shintani* Chuo University, School of Science, 1-13-27, Kasuga Bunkyo 112-0003 Tokyo, Japan Keywords: Nitric Oxide; Peroxynitrite; Measurement; Macrophage The Measurement of NO Produced by Endothelial Cells Introduction Protocol Although there is much interest in NO (nitric oxide) and 1. Perfuse bovine aortic endothelial cells confluently cultured on peroxynitrite (OONO), their measurement in biological media is a cover slip (15 mmφ), with L-arginine solution (L-arg, MW = difficult because of their short lifetimes and low concentrations. Here, 174.2, 50 μM). the use of an NO-sensitive electrode is first described for direct real- 2. Place NO electrode as close as possible to the cover slip without time measurement of NO in endothelial cells. A method for detecting making contact. Start recording the basal level of electrode peroxynitrite produced by the macrophage is also given. Brief current and wait until the current has stabilized (ca 30 min). references to other methods are included in the comments sections. 3. Switch the perfusate to 1 mM ATP/50 mM L-arg solution to NO measurement with NO-sensitive electrodes stimulate endothelial cells. ATP (Mr = 551) should be stored at -20oC. Calibration [1] 4. Re-switch the perfusate to 50 μM L-arf solution and confirm Protocol that the current returns to the basal level.
    [Show full text]
  • The Signaling Pathways and Cross Communication Between the Three Gasotransmitters Nitric Oxide, Carbon Monoxide and Hydrogen Sulfide in Our Vascular System
    The signaling pathways and cross communication between the three gasotransmitters Nitric Oxide, Carbon Monoxide and Hydrogen Sulfide in our vascular system. Bachelor thesis Gun van der, Z.M. (S3225577) June 2019, UMC Groningen Life Science & Technology – medical pharmaceutical sciences Supervisor: Deelman, L.E. Department of clinical pharmacy and pharmacology Content Abstract ................................................................................................................................................... 3 1. Introduction ........................................................................................................................................ 3 2. Gasotransmitter production and signaling .......................................................................................... 4 2.1 Nitric oxide .................................................................................................................................... 4 2.2 Carbon monoxide .......................................................................................................................... 6 2.3 Hydrogen sulfide ........................................................................................................................... 7 3. Cross communication .......................................................................................................................... 9 3.1 Nitric oxide & carbon monoxide.................................................................................................... 9 3.2 Nitric
    [Show full text]
  • 1 the Evolution of Gasotransmitter Biology and Medicine Rui "Wang
    1 The Evolution of Gasotransmitter Biology and Medicine From Atmospheric Toxic Gases to Endogenous Gaseous Signaling Molecules Rui "Wang CONTENTS INTRODUCTION PRODUCTION AND HEALTH HAZARDS OF ATMOSPHERIC GASES PRODUCTION AND PHYSIOLOGICAL EFFECTS OF ENDOGENOUS GASES GASOTRANSMITTERS IN EVOLUTION GASOTRANSMITTERS: DEFINITION OF THE CONCEPT GASOTRANSMITTERS AND ION CHANNELS PERSPECTIVES ON GASOTRANSMITTER RESEARCH ApPENDIX REFERENCES SUMMARY Overproduction of many atmospheric gases, from natural resources and anthropo­ genic activities, impose a serious environmental concern with adverse health effects. Among pollutant gases are nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Over several decades, studies from numerous laboratories have demon­ strated that gases such as NO, CO, and H2S not only are generated in the human body but also play important physiological roles. These particular gases share many common features in their production and function but carryon their tasks in unique ways, which differ from classic signaling molecules, in the human body. Collectively, these endog­ enous molecules of gases or gaseous signaling molecules compose a family of "gasotransmitters." The regulation of ion channels by gasotransmitters, either directly via chemical modification of ion channel proteins or indirectly via second messengers, exerts significant influence on cellular functions. S-nitrosylation, carboxylation, and sulfuration may represent mechanisms of direct interaction of NO, CO, and H2S with ion channel proteins, respectively. From: Signal Transduction and the Gasotransmitters: NO, CO, and H2S in Biology and Medicine Edited by: Rui Wang © Humana Press Inc., Totowa, NJ 3 4 Wang This chapter summarizes the history and evolution ofthe concept of the gasotransmitter and outlines the criteria used to identify novel gasotransmitters.
    [Show full text]