DOCSLIB.ORG

Mitochondrial Dysfunction Mediated by Quinone Oxidation Products of Dopamine: Implications in Dopamine Cytotoxicity and Pathogenesis of Parkinson's Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mitochondrial Dysfunction Mediated by Quinone Oxidation Products of Dopamine: Implications in Dopamine Cytotoxicity and Pathogenesis of Parkinson's Disease CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1812 (2011) 663–673 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbadis Mitochondrial dysfunction mediated by quinone oxidation products of dopamine: Implications in dopamine cytotoxicity and pathogenesis of Parkinson's disease Sirsendu Jana a, Maitrayee Sinha a, Dalia Chanda a, Tapasi Roy a, Kalpita Banerjee a, Soumyabrata Munshi a, Birija S. Patro b, Sasanka Chakrabarti a,⁎ a Department of Biochemistry, Institute of Post-graduate Medical Education & Research, 244, A J C Bose Road, Kolkata, India b Bio-organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India article info abstract Article history: The study has demonstrated that dopamine induces membrane depolarization and a loss of phosphorylation Received 26 September 2010 capacity in dose-dependent manner in isolated rat brain mitochondria during extended in vitro incubation Received in revised form 31 December 2010 and the phenomena are not prevented by oxyradical scavengers or metal chelators. Dopamine effects on brain Accepted 25 February 2011 mitochondria are, however, markedly prevented by reduced glutathione and N-acetyl cysteine and promoted Available online 4 March 2011 by tyrosinase present in the incubation medium. The results imply that quinone oxidation products of dopamine are involved in mitochondrial damage under this condition. When PC12 cells are exposed to Keywords: – μ Dopamine dopamine in varying concentrations (100 400 M) for up to 24 h, a pronounced impairment of mitochondrial Parkinson's disease bio-energetic functions at several levels is observed along with a significant (nearly 40%) loss of cell viability Mitochondria with features of apoptotic nuclear changes and increased activities of caspase 3 and caspase 9 and all these Quinone effects of dopamine are remarkably prevented by N-acetyl cysteine. N-acetyl cysteine also blocks nearly Apoptosis completely the dopamine induced increase in reactive oxygen species production and the formation of Oxidative stress quinoprotein adducts in mitochondrial fraction within PC12 cells and also the accumulation of quinone products in the culture medium. Clorgyline, an inhibitor of MAO-A, markedly decreases the formation of reactive oxygen species in PC12 cells upon dopamine exposure but has only mild protective actions against quinoprotein adduct formation, mitochondrial dysfunctions, cell death and caspase activation induced by dopamine. The results have indicated that quinone oxidation products and not reactive oxygen species are primarily involved in cytotoxic effects of dopamine and the mitochondrial impairment plays a central role in the latter process. The data have clear implications in the pathogenesis of Parkinson's disease. © 2011 Elsevier B.V. All rights reserved. 1. Introduction available dopamine (DA) in nigral neurons can undergo autoxidation or enzyme catalyzed oxidation to produce reactive oxygen species The dopaminergic neuronal death in Parkinson's disease (PD) may (ROS) and an array of toxic quinones and both these groups of involve a complex interplay of genetic and extra-genetic mechanisms compounds have been implicated in the pathogenesis of PD [10–12]. but mitochondrial dysfunction and oxidative stress are thought to be The toxic effects of DA which have been extensively studied on crucial in this process as indicated from studies in experimental cultured cells of neural origin or on isolated brain mitochondria or in models and analysis of post mortem brain samples of PD patients animal models are, therefore, of physiological significance and such [1–4]. Experimental models of PD have utilized both animals and systems serve as useful tools to understand PD pathogenesis [13–19]. cultured cells exposed to various toxins like MPTP (N-methyl-4- Dopamine induced apoptosis has been consistently shown in some of phenyl-1,2,3,6-tetrahydropyridine), 6-hydroxy dopamine or rotenone these models and post-mortem studies have also demonstrated the to induce neuronal death in which oxidative stress, mitochondrial features of apoptosis in PD brains and thus these models have been impairment and apoptosis have been implicated [5–9]. Although these validated to an extent in explaining PD pathogenesis or searching for models are useful, MPTP, rotenone and 6-hydroxy dopamine are new therapeutic targets [20–23]. However, many uncertainties exist as not endogenously available and as such it is not clear whether the to the mediators and mechanisms of DA induced cell death in such proposed mechanisms of actions of these toxins really represent models. Apart from mitochondrial impairment, the inactivation of the in vivo scenario in sporadic PD. On the other hand endogenously proteasomal activity or the activation of nuclear factor-κB (NF-κB) or various mitogen-activated protein kinase (MAPK) pathways like p38 family of kinases or c-Jun N-terminal kinases (JNK) has also been ⁎ Corresponding author. Tel.: +91 33 22234413/+91 9874489805. implicated in DA-induced cytotoxicity and likewise the involvement of E-mail address: [email protected] (S. Chakrabarti). autophagic and necrotic death instead of apoptosis has been suggested 0925-4439/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.bbadis.2011.02.013 664 S. Jana et al. / Biochimica et Biophysica Acta 1812 (2011) 663–673 in several studies [24–31]. The relative contributions of ROS and toxic within mitochondria driven by the negative transmembrane potential quinones in DA mediated cytotoxicity also remain unresolved, and forms concentration dependent J-aggregates. When excited at although this information may be critical in developing or screening 490 nm, the monomeric form of the dye emits at 527 nm while the neuroprotective drugs for PD using such model systems. J-aggregates show maximum emission at 590 nm [37,38].Briefly, Although many studies have demonstrated the importance of ROS an aliquot of mitochondria (control or DA-treated or DA-treated in in DA cytotoxicity in experimental models, the antioxidants like the presence of other additions) was incubated at 37 °C for 30 min in vitamin C and vitamin E and the enzymes like SOD and catalase have isotonic buffer A containing 10 mM pyruvate, 10 mM succinate and variable protective effects in such systems and the use of antioxidants 1mMADPinthepresenceof5μM JC-1. At the end of the incubation, the have met with near complete failure as neuroprotective agents in dye loaded mitochondria were collected by centrifugation, washed PD in clinical trials [22,26,32]. On the other hand the role of toxic extensively with isotonic buffer A to remove the excess dye from outside quinones in DA induced neuronal damage has been studied in a and then resuspended in the same buffer in appropriate dilution, relatively few studies, although these reactive nucleophiles have been followed by the measurement of strong red fluorescence of J-aggregates shown to damage various brain sub-cellular components including (λex 490 nm, λem 590 nm) in a spectrofluorometer (FP 6300, JASCO mitochondria and inactivate different enzymes during in vitro International Co., Japan). incubation [12,19,33–36]. The present study has been undertaken to critically review the damaging effects of DA on isolated mitochondria 2.4. Measurement of phosphorylation capacity of rat brain mitochondria with regard to the involvement of ROS and toxic quinones as an after DA treatment extension of our earlier published work and further to examine if similar mechanisms are also operative when intact rat pheochromo- The mitochondrial phosphate utilization was assayed following the cytoma (PC12) cells are exposed to DA. In addition the consequences method published earlier [39,40].Briefly, in a total volume of 500 μlina of DA effects on mitochondrial bioenergetics in the context of cell medium containing 125 mM KCl, 75 mM sucrose, 0.1 mM EGTA, 1 mM death and apoptosis have been worked out and agents that can block MgCl2, 10 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic these processes have also been tested. The results of this study are acid), 2 mM phosphate, 0.3% BSA (bovine serum albumin), 0.5 mM ADP, therefore relevant not only in understanding the etiopathogenesis 5 mM pyruvate, 10 mM succinate and 10 mM glucose was added of PD but also in finding suitable neuroprotective agents against this an aliquot of 50 μl mitochondrial suspension (control or DA-treated or disease condition. DA-treated in the presence of other additions) containing 100–150 μgof protein, followed by the immediate addition of 5 units of hexokinase 2. Materials and methods (Sigma Aldrich, USA) and the incubation was continued at 37 °C for 30 min. The incubation was terminated by the addition of 5% ice cold 2.1. Animals TCA (trichloroacetic acid) and the amount of inorganic phosphate estimated spectrophotometrically using a reaction based on the Young albino rats of ‘Charles–Foster’ strain (5–6 months old, body reduction of phosphomolybdate as described earlier [34].A‘0’-min weight 120–150 g) kept on commercially available laboratory chow sample was also assayed for inorganic phosphate content where and water ad libitum were used in this study. The animals were hexokinase addition was immediately followed by the treatment with maintained and used as per the regulations and guidelines of the 5% ice-cold TCA. The difference in inorganic phosphate content between ‘Animal Ethical Committee’ of the Institute. 0 and 30 min samples was calculated to estimate the phosphorylation capacity of brain mitochondria. Glucose and ADP in the reaction mixture 2.2. Isolation of rat brain mitochondria and incubation with DA were used as a trap for ATP to maintain the level of ADP in the system as also to prevent the release of free inorganic phosphate from ATP by Rat brain mitochondria were isolated by a method based on the action of various phosphatases. differential centrifugation with digitonin treatment as published earlier [16,19]. The final mitochondrial pellet was suspended in 2.5.
Load more

Recommended publications
  • Orbital-Dependent Redox Potential Regulation of Quinone Derivatives For
    RSC Advances View Article Online PAPER View Journal | View Issue Orbital-dependent redox potential regulation of quinone derivatives for electrical energy storage† Cite this: RSC Adv.,2019,9,5164 Zhihui Niu,‡ab Huaxi Wu,‡a Yihua Lu,b Shiyun Xiong,a Xi Zhu,*b Yu Zhao *a and Xiaohong Zhang*a Electrical energy storage in redox flow batteries has received increasing attention. Redox flow batteries using organic compounds, especially quinone-based molecules, as active materials are of particular interest owing to the material sustainability, tailorable redox properties, and environmental friendliness of quinones and their derivatives. In this report, various quinone derivatives were investigated to determine their suitability for applications in organic RFBs. Moreover, the redox potential could be internally Received 14th November 2018 regulated through the tuning of s and p bonding contribution at the redox-active sites. Furthermore, the Accepted 22nd January 2019 binding geometry of some selected quinone derivatives with metal cations was studied. These studies DOI: 10.1039/c8ra09377f provide an alternative strategy to identify and design new quinone molecules with suitable redox rsc.li/rsc-advances potentials for electrical energy storage in organic RFBs. Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Introduction include electrolyte corrosivity, poor redox kinetics, high mate- rial cost, and relatively low efficiency, which prevent their large- The development of renewable energy technologies that are not scale commercialization.9,10
    [Show full text]
  • Synthesis and Chemistry of Naphthalene Annulated Trienyl Iron Complexes: Potential Anticancer DNA Alkylation Reagents Traci Means University of Arkansas, Fayetteville
    Inquiry: The University of Arkansas Undergraduate Research Journal Volume 3 Article 18 Fall 2002 Synthesis and Chemistry of Naphthalene Annulated Trienyl Iron Complexes: Potential Anticancer DNA Alkylation Reagents Traci Means University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/inquiry Part of the Medical Biochemistry Commons, and the Organic Chemistry Commons Recommended Citation Means, Traci (2002) "Synthesis and Chemistry of Naphthalene Annulated Trienyl Iron Complexes: Potential Anticancer DNA Alkylation Reagents," Inquiry: The University of Arkansas Undergraduate Research Journal: Vol. 3 , Article 18. Available at: http://scholarworks.uark.edu/inquiry/vol3/iss1/18 This Article is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Inquiry: The nivU ersity of Arkansas Undergraduate Research Journal by an authorized editor of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. Means: Synthesis and Chemistry of Naphthalene Annulated Trienyl Iron Co 120 INQUIRY Volume 3 2002 SYNTHESIS AND CHEMISTRY OF NAPHTHALENE ANNULATED TRIENYL IRON COMPLEXES: POTENTIAL ANTICANCER DNA ALKYLATION REAGENTS Traci Means Department of Chemistry and Bioc~emistry Fulbright College of Arts and Sctences Mentor: Dr. Neil T. Allison Department of Chemistry and Biochemistry Abstract: is mainly electrophilic in nature, which can also be directly correlated to their toxicological properties. If the alkylation Iron complex chemistry that opens a new door to the process is achieved under mild, ideally biological, conditions, it medicinal and pharmaceutical worlds is the aim ofthis research. could be used in a number ofbiomolecular applications. In fact, Specifically, ortho-quinone methide moieties are intermediates these reactive intermediates have been used as DNA alkylating in several antitumor drugs and have been identified as agents and crosslinkers.1 Compounds that react through quinone bioreductive alkylators ofDNA.
    [Show full text]
  • Catechol Ortho-Quinones: the Electrophilic Compounds That Form Depurinating DNA Adducts and Could Initiate Cancer and Other Diseases
    Carcinogenesis vol.23 no.6 pp.1071–1077, 2002 Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases Ercole L.Cavalieri1,3, Kai-Ming Li1, Narayanan Balu1, elevated level of reactive oxygen species, a condition known Muhammad Saeed1, Prabu Devanesan1, as oxidative stress (1,2). As electrophiles, catechol quinones Sheila Higginbotham1, John Zhao2, Michael L.Gross2 and can form covalent adducts with cellular macromolecules, Eleanor G.Rogan1 including DNA (4). These are stable adducts that remain in DNA unless removed by repair and depurinating ones that are 1Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, released from DNA by destabilization of the glycosyl bond. NE 68198-6805 and 2Department of Chemistry, Washington University, Thus, DNA can be damaged by the reactive quinones them- One Brookings Drive, St Louis, MO 63130, USA selves and by reactive oxygen species (hydroxyl radicals) 3To whom correspondence should be addressed (1,4,5). The formation of depurinating adducts by CE quinones Email: [email protected] reacting with DNA may be a major event in the initiation of Catechol estrogens and catecholamines are metabolized to breast and other human cancers (4,5). The depurinating adducts quinones, and the metabolite catechol (1,2-dihydroxyben- are released from DNA, leaving apurinic sites in the DNA zene) of the leukemogenic benzene can also be oxidized to that can generate
    [Show full text]
  • Investigation of Microbial Interactions and Ecosystem
    INVESTIGATION OF MICROBIAL INTERACTIONS AND ECOSYSTEM DYNAMICS IN A LOW O2 CYANOBACTERIAL MAT by Alexander A. Voorhies A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Earth and Environmental Sciences) in The University of Michigan 2014 Doctoral Committee: Assistant Professor Gregory J. Dick, Chair Associate Professor Matthew R. Chapman Assistant Professor Vincent J. Denef Professor Daniel C. Fisher Associate Professor Nathan D. Sheldon © Alexander A. Voorhies 2014 DEDICATION To my wife Hannah ii ACKNOWLEDGEMENTS Funding for the research presented here was provided by the National Science Foundation, the University of Michigan CCMB Pilot Grant, and a Scott Turner research award from the University of Michigan Earth and Environmental Sciences Department. I am grateful for the opportunities to explore my scientific interests this funding has made possible. I would like to acknowledge my co-authors and collaborators, who offered advice, guidance and immeasurable assistance throughout this process. Gregory J. Dick, Bopi Biddanda, Scott T. Kendall, Sunit Jain, Daniel N. Marcus, Stephen C. Nold and Nathan D. Sheldon are co- authors on CHAPTER II, which was published in Geobiology in 2012; Gregory J. Dick was a co-author on CHAPTER III, which is in preparation for publication; and Gregory J. Dick, Sarah D. Eisenlord, Daniel N. Marcus, Melissa B. Duhaime, Bopaiah A. Biddanda and James D Cavalcoli are co-authors on Chapter IV, which is in preparation for publication. I thank my committee members: Matt Chapman, Nathan Sheldon, Vincent Denef and Dan Fisher. Their input and guidance throughout my graduate studies has kept me on track and made significant enhancements to this dissertation.
    [Show full text]
  • The Respiratory Chain & Oxidative Phosphorylation
    ch12.qxd 2/13/2003 2:46 PM Page 92 The Respiratory Chain & Oxidative Phosphorylation 12 Peter A. Mayes, PhD, DSc, & Kathleen M. Botham, PhD, DSc BIOMEDICAL IMPORTANCE trapping the liberated free energy as high-energy phos- phate, and the enzymes of β-oxidation and of the citric Aerobic organisms are able to capture a far greater pro- acid cycle (Chapters 22 and 16) that produce most of portion of the available free energy of respiratory sub- the reducing equivalents. strates than anaerobic organisms. Most of this takes place inside mitochondria, which have been termed the “powerhouses” of the cell. Respiration is coupled to the Components of the Respiratory Chain generation of the high-energy intermediate, ATP, by Are Arranged in Order of Increasing oxidative phosphorylation, and the chemiosmotic Redox Potential theory offers insight into how this is accomplished. A number of drugs (eg, amobarbital) and poisons (eg, Hydrogen and electrons flow through the respiratory chain (Figure 12–3) through a redox span of 1.1 V cyanide, carbon monoxide) inhibit oxidative phos- + phorylation, usually with fatal consequences. Several in- from NAD /NADH to O2/2H2O (Table 11–1). The herited defects of mitochondria involving components respiratory chain consists of a number of redox carriers of the respiratory chain and oxidative phosphorylation that proceed from the NAD-linked dehydrogenase sys- have been reported. Patients present with myopathy tems, through flavoproteins and cytochromes, to mole- and encephalopathy and often have lactic acidosis. cular oxygen. Not all substrates are linked to the respi- ratory chain through NAD-specific dehydrogenases; some, because their redox potentials are more positive SPECIFIC ENZYMES ACT AS MARKERS (eg, fumarate/succinate; Table 11–1), are linked di- rectly to flavoprotein dehydrogenases, which in turn are OF COMPARTMENTS SEPARATED BY linked to the cytochromes of the respiratory chain (Fig- THE MITOCHONDRIAL MEMBRANES ure 12–4).
    [Show full text]
  • Investigating PAH Relative Reactivity Using Congener Profiles, Quinone Measurements and Back Trajectories
    Open Access Discussion Paper | Discussion Paper | Discussion Paper | Discussion Paper | Atmos. Chem. Phys. Discuss., 13, 25741–25768, 2013 Atmospheric www.atmos-chem-phys-discuss.net/13/25741/2013/ Chemistry doi:10.5194/acpd-13-25741-2013 © Author(s) 2013. CC Attribution 3.0 License. and Physics Discussions This discussion paper is/has been under review for the journal Atmospheric Chemistry and Physics (ACP). Please refer to the corresponding final paper in ACP if available. Investigating PAH relative reactivity using congener profiles, quinone measurements and back trajectories M. S. Alam1, J. M. Delgado-Saborit1, C. Stark1, and R. M. Harrison1,2 1Division of Environmental Health & Risk Management School of Geography, Earth & Environmental Sciences University of Birmingham Edgbaston, Birmingham, B15 2TT, UK 2Department of Environmental Sciences/Center of Excellence in Environmental Studies, King Abdulaziz University, Jeddah, 21589, Saudi Arabia Received: 22 July 2013 – Accepted: 12 September 2013 – Published: 8 October 2013 Correspondence to: R. M. Harrison ([email protected]) Published by Copernicus Publications on behalf of the European Geosciences Union. 25741 Discussion Paper | Discussion Paper | Discussion Paper | Discussion Paper | Abstract Vapour and particle-associated concentrations of 15 polycyclic aromatic hydrocarbons (PAH) and 11 PAH quinones have been measured in winter and summer campaigns at the rural site, Weybourne in eastern England. Concentrations of individual PAH are 20– 5 140 times smaller than average concentrations at an English urban site. The concen- trations of PAH are greatest in air masses originating from southern England relative to those from Scandinavia and the North Atlantic, while quinone to parent PAH ratios show an inverse behaviour, being highest in the more aged North Atlantic polar air masses.
    [Show full text]
  • Boom Clay Natural Organic Matter
    EXTERNAL REPORT SCK•CEN-ER-206 12/CBr/P-37 Boom Clay natural organic matter Status Report 2011 Christophe Bruggeman and Mieke De Craen SCK•CEN Contract: CO-90-08-2214-00 NIRAS/ONDRAF contract: CCHO 2009- 0940000 Research Plan Geosynthesis June, 2012 SCK•CEN RDD Boeretang 200 BE-2400 Mol Belgium EXTERNAL REPORT OF THE BELGIAN NUCLEAR RESEARCH CENTRE SCK•CEN-ER-206 12/CBr/P-37 Boom Clay natural organic matter Status Report 2011 Christophe Bruggeman and Mieke De Craen SCK•CEN Contract: CO-90-08-2214-00 NIRAS/ONDRAF contract: CCHO 2009- 0940000 Research Plan Geosynthesis June, 2012 Status: Unclassified ISSN 1782-2335 SCK•CEN Boeretang 200 BE-2400 Mol Belgium © SCK•CEN Studiecentrum voor Kernenergie Centre d’étude de l’énergie Nucléaire Boeretang 200 BE-2400 Mol Belgium Phone +32 14 33 21 11 Fax +32 14 31 50 21 http://www.sckcen.be Contact: Knowledge Centre [email protected] COPYRIGHT RULES All property rights and copyright are reserved to SCK•CEN. In case of a contractual arrangement with SCK•CEN, the use of this information by a Third Party, or for any purpose other than for which it is intended on the basis of the contract, is not authorized. With respect to any unauthorized use, SCK•CEN makes no representation or warranty, expressed or implied, and assumes no liability as to the completeness, accuracy or usefulness of the information contained in this document, or that its use may not infringe privately owned rights. SCK•CEN, Studiecentrum voor Kernenergie/Centre d'Etude de l'Energie Nucléaire Stichting van Openbaar Nut – Fondation d'Utilité Publique ‐ Foundation of Public Utility Registered Office: Avenue Herrmann Debroux 40 – BE‐1160 BRUSSEL Operational Office: Boeretang 200 – BE‐2400 MOL Table of Contents Abstract .....................................................................................................................................
    [Show full text]
  • Building and Identifying Highly Active Oxygenated Groups in Carbon
    ARTICLE https://doi.org/10.1038/s41467-020-15782-z OPEN Building and identifying highly active oxygenated groups in carbon materials for oxygen reduction to H2O2 ✉ Gao-Feng Han 1, Feng Li 1 , Wei Zou2, Mohammadreza Karamad3, Jong-Pil Jeon1, Seong-Wook Kim1, ✉ Seok-Jin Kim 1, Yunfei Bu 4, Zhengping Fu2,5, Yalin Lu 2,5, Samira Siahrostami 6 & ✉ Jong-Beom Baek 1 1234567890():,; The one-step electrochemical synthesis of H2O2 is an on-site method that reduces depen- dence on the energy-intensive anthraquinone process. Oxidized carbon materials have pro- ven to be promising catalysts due to their low cost and facile synthetic procedures. However, the nature of the active sites is still controversial, and direct experimental evidence is pre- sently lacking. Here, we activate a carbon material with dangling edge sites and then decorate them with targeted functional groups. We show that quinone-enriched samples exhibit high selectivity and activity with a H2O2 yield ratio of up to 97.8 % at 0.75 V vs. RHE. Using density functional theory calculations, we identify the activity trends of different possible quinone functional groups in the edge and basal plane of the carbon nanostructure and determine the most active motif. Our findings provide guidelines for designing carbon-based catalysts, which have simultaneous high selectivity and activity for H2O2 synthesis. 1 School of Energy and Chemical Engineering/Center for Dimension-Controllable Organic Frameworks, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea. 2 CAS Key Laboratory of Materials for Energy Conversion, Department of Materials Science and Engineering, University of Science and Technology of China (USTC), 230026 Hefei, P.
    [Show full text]
  • Oxidation of Hydrogen Sulfide by Quinones
    International Journal of Molecular Sciences Article Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects Kenneth R. Olson 1,2,* , Yan Gao 1 and Karl D. Straub 3,4 1 Indiana University School of Medicine—South Bend Center, South Bend, IN 46617, USA; [email protected] 2 Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA 3 Central Arkansas Veteran’s Healthcare System, Little Rock, AR 72205, USA; [email protected] 4 Departments of Medicine and Biochemistry, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA * Correspondence: [email protected]; Tel.: +1-(574)-631-7560; Fax: +1-(574)-631-7821 Abstract: We have shown that autoxidized polyphenolic nutraceuticals oxidize H2S to polysulfides and thiosulfate and this may convey their cytoprotective effects. Polyphenol reactivity is largely at- tributed to the B ring, which is usually a form of hydroxyquinone (HQ). Here, we examine the effects of HQs on sulfur metabolism using H2S- and polysulfide-specific fluorophores (AzMC and SSP4, respectively) and thiosulfate sensitive silver nanoparticles (AgNP). In buffer, 1,4-dihydroxybenzene (1,4-DB), 1,4-benzoquinone (1,4-BQ), pyrogallol (PG) and gallic acid (GA) oxidized H2S to polysul- fides and thiosulfate, whereas 1,2-DB, 1,3-DB, 1,2-dihydroxy,3,4-benzoquinone and shikimic acid did not. In addition, 1,4-DB, 1,4-BQ, PG and GA also increased polysulfide production in HEK293 cells. In buffer, H2S oxidation by 1,4-DB was oxygen-dependent, partially inhibited by tempol and trolox, and absorbance spectra were consistent with redox cycling between HQ autoxidation and H2S-mediated reduction.
    [Show full text]
  • Electrochemical Response of Glucose Oxidase Adsorbed on Laser-Induced Graphene
    nanomaterials Article Electrochemical Response of Glucose Oxidase Adsorbed on Laser-Induced Graphene Sónia O. Pereira * , Nuno F. Santos, Alexandre F. Carvalho, António J. S. Fernandes and Florinda M. Costa i3N, Department of Physics, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] (N.F.S.); [email protected] (A.F.C.); [email protected] (A.J.S.F.); fl[email protected] (F.M.C.) * Correspondence: [email protected] Abstract: Carbon-based electrodes have demonstrated great promise as electrochemical transducers in the development of biosensors. More recently, laser-induced graphene (LIG), a graphene derivative, appears as a great candidate due to its superior electron transfer characteristics, high surface area and simplicity in its synthesis. The continuous interest in the development of cost-effective, more stable and reliable biosensors for glucose detection make them the most studied and explored within the academic and industry community. In this work, the electrochemistry of glucose oxidase (GOx) adsorbed on LIG electrodes is studied in detail. In addition to the well-known electroactivity of free flavin adenine dinucleotide (FAD), the cofactor of GOx, at the expected half-wave potential of −0.490 V vs. Ag/AgCl (1 M KCl), a new well-defined redox pair at 0.155 V is observed and shown to be related to LIG/GOx interaction. A systematic study was undertaken in order to understand the origin of this activity, including scan rate and pH dependence, along with glucose detection tests. Citation: Pereira, S.O.; Santos, N.F.; Two protons and two electrons are involved in this reaction, which is shown to be sensitive to the Carvalho, A.F.; Fernandes, A.J.S.; concentration of glucose, restraining its origin to the electron transfer from FAD in the active site of Costa, F.M.
    [Show full text]
  • Quinone Lit Talk
    Quinones in Organic Chemistry: Synthesis of and Applications Towards Natural Products H3C CH3 H H H3C OH H OH O N CH3 O CH3 O HO O Tetrapetalone A (revised structure) TL, 2003, 44, 7417 Literature Presentation Ryan Zeidan Stoltz Group Meeting 2/16/04 Outline of Quinones I. Introduction to Quinones A. Nomenclature B. Biochemistry C. Biosynthesis II. Synthesis of Quinones via Oxidation A. Fremy's Salt B. CAN C. LTA D. DDQ E. Air III. Other Syntheses of Quinones/Uses A. Boronic Esters B. Indoles C. DMP oxidation of anilides D. Cyclobutenediones E. Benzoin reaction IV. Applications to Natural Products A. Aflatoxin B B. Elisabethin A C. Lemonomycin 1 Quinone Background - Nomenclature OH OH O O O OH O Phenol Hydroquinone p-Quinone o-Quinone O O O R N R OH Quinol o-Quinone methide p-Quinone methide o-Quinone methide imine Redox Process -2e- Hydroquinone Quinone + 2 H+ 2e- O H O O - H - H H H O H O H O hydroquinone semiquinone quinone OH O OH O Jones AgO2 SnCl or SnCl2 2 O NaBH4 OH OH O 2 Quinones in Nature - Ubiquinones mediate electron transfer processes involved in energy production through their redox reactions: O OH MeO Me MeO Me + NAD+ NADH + H+ + Reduced MeO R MeO R Oxidized form form O OH OH O MeO Me MeO Me + 1/2 O 2 + H2O MeO R MeO R OH O + NAD+ + H O Net Change: NADH + 1/2 O2 + H 2 Biosynthesis of Quinones: Pentaketides O O O OH OH SCoA O O O O O O CoAS O HO OH O O OH O HO OH O O O O MeO OMe O O O SCoA O OH O 3 Biosynthesis Continued Heptaketides: O OH O O O HO OMe HO OMe O O O O O O SCoA O O O OH O O Octaketides: OH O Me OH OH Me O O NADH NAD+ O O O SCoA O O O O O O O O O H O O OH OH Me OH O Me O O O HO O HO O O A Representative Difficulty in Direct Oxidation of Arenes O Br Br Br Br O HNO3 H2SO4 Fremy's salt NO2 OH Br Br 1.
    [Show full text]
  • Polycyclic Aromatic Hydrocarbons (Pahs) and to Emphasize the Human Health Effects That May Result from Exposure to Them
    TOXICOLOGICAL PROFILE FOR POLYCYCLIC AROMATIC HYDROCARBONS U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry August 1995 PAHs ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. PAHs iii UPDATE STATEMENT A Toxicological Profile for Polycyclic Aromatic Hydrocarbons was released in December 1990. This edition supersedes any previously released draft or final profile. Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 PAHs 1 1. PUBLIC HEALTH STATEMENT This statement was prepared to give you information about polycyclic aromatic hydrocarbons (PAHs) and to emphasize the human health effects that may result from exposure to them. The Environmental Protection Agency (EPA) has identified 1,408 hazardous waste sites as the most serious in the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for long-term federal clean-up activities. PAHs have been found in at least 600 of the sites on the NPL. However, the number of NPL sites evaluated for PAHs is not known. As EPA evaluates more sites, the number of sites at which PAHs are found may increase. This information is important because exposure to PAHs may cause harmful health effects and because these sites are potential or actual sources of human exposure to PAHs.
    [Show full text]