A Comprehensive Review Article on Isoprostanes As Biological Markers
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Non-Cyclooxygenase-Derived Prostanoids (F2-Isoprostanes) Are Formed in Situ on Phospholipids (Eicosanoids/Lipids/Oxidative Stress/Peroxidation/Free Radicals) JASON D
Proc. Nail. Acad. Sci. USA Vol. 89, pp. 10721-10725, November 1992 Pharmacology Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids (eicosanoids/lipids/oxidative stress/peroxidation/free radicals) JASON D. MORROW, JOSEPH A. AWAD, HOLLIS J. BOSS, IAN A. BLAIR, AND L. JACKSON ROBERTS II* Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, TN 37232.6602 Communicated by Philip Needleman, July 21, 1992 (receivedfor review March 11, 1992) ABSTRACT We recently reported the discovery ofa series the formation ofthese prostanoids occurs independent ofthe of bioactive prostaglandin F2-like compounds (F2-isoprostanes) catalytic activity of the cyclooxygenase enzyme, which had that are produced in vivo by free radical-catalyzed peroxidation been considered obligatory for endogenous prostanoid bio- ofarachidonic acid independent ofthe cyclooxygenase enzyme. synthesis. Circulating levels ofthese compounds were shown Inasmuch as phospholipids readily undergo peroxidation, we to increase dramatically in animal models of free radical examined the possibility that F2-isoprostanes may be formed in injury (8). Interestingly, the levels of these prostanoids in situ on phospholipids. Initial support for this hypothesis was normal human plasma and urine are one or two orders of obtained by the rmding that levels of free F2-isoprostanes magnitude higher than those of prostaglandins produced by measured after hydrolysis oflipids extracted from livers ofrats the cyclooxygenase enzyme. Formation ofthese compounds treated with CCI4 to induce lipid peroxidation were more than proceeds through intermediates composed of four positional 100-fold higher than levels in untreated animal. Further, peroxyl radical isomers of arachidonic acid which undergo increased levels of lipid-associated F2-isoprostanes in livers of endocyclization to yield bicyclic endoperoxide PGG2-like CCI4-treated rats preceded the appearance of free compounds compounds. -
Chemical Compositional Changes in Over-Oxidized Fish Oils
foods Article Chemical Compositional Changes in Over-Oxidized Fish Oils 1, 2, 3 3 Austin S. Phung y, Gerard Bannenberg * , Claire Vigor , Guillaume Reversat , Camille Oger 3 , Martin Roumain 4 , Jean-Marie Galano 3, Thierry Durand 3, 4 2, 5, Giulio G. Muccioli , Adam Ismail z and Selina C. Wang * 1 Department of Chemistry, University of California, Davis, CA 95616, USA; [email protected] 2 Global Organization for EPA and DHA Omega-3s (GOED), Salt Lake City, UT 84105, USA; [email protected] 3 Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université de Montpellier, ENSCM, 34093 Montpellier, France; [email protected] (C.V.); [email protected] (G.R.); [email protected] (C.O.); [email protected] (J.-M.G.); [email protected] (T.D.) 4 Louvain Drug Research Institute, Université Catholique de Louvain, 1200 Brussels, Belgium; [email protected] (M.R.); [email protected] (G.G.M.) 5 Department of Food Science and Technology, University of California, Davis, CA 95616, USA * Correspondence: [email protected] (G.B.); [email protected] (S.C.W.) Present address: Visby Medical Inc., 3010 N. First Street, San Jose, CA 95134, USA. y Present address: KD Pharma, Am Kraftwerk 6, D 66450 Bexbach, Germany. z Received: 16 September 2020; Accepted: 16 October 2020; Published: 20 October 2020 Abstract: A recent study has reported that the administration during gestation of a highly rancid hoki liver oil, obtained by oxidation through sustained exposure to oxygen gas and incident light for 30 days, causes newborn mortality in rats. -
Molecular Details of Prostaglandin Synthesis Catalyzed by Cyclooxygenase-2 and Its Inhibition by Aspirin
ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Molecular Details of Prostaglandin Synthesis Catalyzed by Cyclooxygenase-2 and Its Inhibition by Aspirin. Anna Cebrián Prats PhD program in Chemistry Supervisors: José Maria Lluch López Àngels González Lafont Departament de Química Facultad de Cièncias 2020 This is an article-based PhD Thesis. This dissertation is composed of a short overview of the work, followed by a copy of the papers already published. “But nature is always more subtle, more intricate, more elegant than what we are able to imagine.” Carl Sagan Contents List of Acronyms . v I Introduction 1 1 Introduction 3 1.1 Biological Overview . 3 1.1.1 Polyunsaturated Fatty Acids (PUFAs) . 4 1.1.2 Eicosanoids . 5 1.1.3 Prostanoids . 6 1.1.4 Role of PUFAs into inflammatory processes . 7 1.2 Prostaglandin Endoperoxide H Synthase . 9 1.2.1 PGHS-2 structure . 10 1.2.2 Substrates binding to COX active site . 11 1.3 Catalytic Reaction . 13 1.3.1 Reaction Mechanism in the COX active site . 14 1.3.2 Regioselectivity and Stereoselectiviy . -
Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators On
antioxidants Review Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation 1, 1,2, 2, Gyeoung Jin Kang y, Eun Ji Kim y and Chang Hoon Lee * 1 Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] (G.J.K.); [email protected] (E.J.K.) 2 College of Pharmacy, Dongguk University, Seoul 04620, Korea * Correspondence: [email protected]; Tel.: +82-31-961-5213 Equally contributed. y Received: 11 November 2020; Accepted: 9 December 2020; Published: 10 December 2020 Abstract: Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation. Keywords: cardiac fibrosis; NRF2; lipoxins; resolvins; maresins; neuroprotectins 1. Introduction Cardiovascular disease is the leading cause of death worldwide [1]. Cardiac fibrosis is a major factor leading to the progression of myocardial infarction and heart failure [2]. Cardiac fibrosis is characterized by the net accumulation of extracellular matrix proteins in the cardiac stroma and ultimately impairs cardiac function [3]. Therefore, interest in substances with cardioprotective activity continues. -
Detection of F2-Isoprostanes and F4-Neuroprostanes in Clinical Studies
Mini Review Detection of F2-isoprostanes and F4-neuroprostanes in Clinical Studies Hsiu-Chuan Yen Graduate Institute of Medical Biotechnology Department of Medical Biotechnology and Laboratory Science Chang Gung University, Taoyuan, Taiwan Detecting stable products of oxidative damage is the most reliable approach to access oxidative stress in vivo. F2-isoprostanes (F2-IsoPs) and F4-neuroprostanes (F4-NPs) are the most specific markers of lipid peroxidation, which is superior to other markers of oxidative damage for clinical studies in many ways. F2-IsoPs is formed from peroxidation of arachidonic acid that is abundant in all kind of cells, while F4-NPs is derived from docosahexaenoic acid enriched in neurons. Moreover, F2-IsoPs is known to exhibit biological activities, such as vasoconstriction and platelet aggregation. Gas chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is the reference method and the method with highest sensitivity to quantify F2-IsoPs and F4-NPs. F2-IsoPs is not only a widely used gold marker of lipid peroxidation detectable in all types of body fluids, but also a cause of diseases due to its biological activities, a marker to evaluate severity or predict out- come of diseases, or a tool to monitor the effectiveness of antioxidant therapy. Clinical studies de- tecting F4-NPs are little because cerebrospinal fluid or brain tissues are needed, but it is more useful than F2-IsoPs in selectively evaluating neuronal oxidative damage. This paper will discuss the above issues with emphasis on the advantages and considerations in clinical studies. Key words: Lipid peroxidation, Gas chromatography/negative-ion chemical-ionization mass spectrometry, Body fluid, Neuron The best way to access oxidative stress in humans is to detect specific and stable markers of oxidative dam- Introduction age using reliable methods. -
Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome
Functional Metabolomics Reveals Novel Active Products in the DHA Metabolome The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters. Citation Shinohara, Masakazu, Valbona Mirakaj, and Charles N. Serhan. 2012. Functional metabolomics reveals novel active products in the DHA metabolome. Frontiers in Immunology 3:81. Published Version doi:10.3389/fimmu.2012.00081 Accessed February 19, 2015 10:33:44 AM EST Citable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10366358 Terms of Use This article was downloaded from Harvard University's DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA (Article begins on next page) REVIEW ARTICLE published: 17 April 2012 doi: 10.3389/fimmu.2012.00081 Functional metabolomics reveals novel active products in the DHA metabolome Masakazu Shinohara,Valbona Mirakaj and Charles N. Serhan* Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Edited by: Endogenous mechanisms for successful resolution of an acute inflammatory response and Masaaki Murakami, Osaka University, the local return to homeostasis are of interest because excessive inflammation underlies Japan many human diseases. In this review, we provide an update and overview of functional Reviewed by: Takayuki Yoshimoto,Tokyo Medical metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA). University, Japan Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive Hiroki Yoshida, Saga University products as well as aspirin-triggered forms of protectins (AT-PD1). -
1 Visualizing Molecular Interactions
Visualizing Molecular Interactions: Computational Investigations of Structure-Function Relationships and Dynamics in Biomolecular Systems Kristina E. Furse Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556 Email: [email protected] Computer modeling has emerged as a powerful complement The de novo receptor models also yielded some interesting and to experimental and theoretical investigations. Visualization of testable hypotheses for the structural basis of !-AR subtype experimental data in the context of a three-dimensional, ligand selectivity. atomic-scale model can not only help to explain unexpected Four years after we completed our study, the first high- results but often raises new questions, driving future research. resolution X-ray structure of !-AR was released.3 Many of our Models of sufficient quality can be set in motion in molecular structural predictions were validated by the X-ray structure, dynamics (MD) simulations to move beyond a static picture including an unusual configuration of three active site serines and provide insight into the dynamics of important biological and the unique spatial arrangement of two extracellular processes. disulfide bonds that introduced a previously unknown loop The power of computer modeling and simulation is residue, Phe-193, into the binding site (Figure 1). Our de novo nowhere more evident than in the study of small-molecule models were included in a virtual screening study by an interactions with proteins and DNA. Detailed knowledge of independent lab.4 They found that our model outperformed these molecular-scale interactions is vital to rational drug rhodopsin-based homology models as well as other de novo design, understanding and harnessing the catalytic power of models. -
Cysteinyl Leukotrienes and 8-Isoprostane in Exhaled Breath
505 ASTHMA Thorax: first published as 10.1136/thorax.58.6.509 on 1 June 2003. Downloaded from Cysteinyl leukotrienes and 8-isoprostane in exhaled breath condensate of children with asthma exacerbations E Baraldi, S Carraro, R Alinovi, A Pesci, L Ghiro, A Bodini, G Piacentini, F Zacchello, S Zanconato ............................................................................................................................. Thorax 2003;58:505–509 Background: Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory metabolites derived from arachidonic acid whose levels are increased in the airways of asthmatic patients. Isoprostanes are relatively stable and specific for lipid peroxidation, which makes them potentially reliable biomarkers for oxidative stress. A study was undertaken to evaluate the effect of a course of oral steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of children with an asthma exacerbation. Methods: Exhaled breath condensate was collected and fractional exhaled nitric oxide (FENO) and spirometric parameters were measured before and after a 5 day course of oral prednisone (1 mg/kg/ day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and 8-isoprostane concentrations were measured using an enzyme immunoassay. FENO was measured using a chemiluminescence ana- lyser. Exhaled breath condensate was also collected from 10 healthy children. Results: Before prednisone treatment both Cys-LT and 8-isoprostane concentrations were higher in See end of article for asthmatic subjects (Cys-LTs, 12.7 pg/ml (IQR 5.4–15.6); 8-isoprostane, 12.0 pg/ml (9.4–29.5)) than authors’ affiliations ....................... in healthy children (Cys-LTs, 4.3 pg/ml (2.0–5.7), p=0.002; 8-isoprostane, 2.6 pg/ml (2.1–3.0), p<0.001). -
My Favorite Protein: Cyclooxygenase By: Kristen Huber CH 791A - Biomolecular Structures Craig Martin and Jeanne Hardy December 9, 2005
Huber 1 My Favorite Protein: Cyclooxygenase By: Kristen Huber CH 791A - Biomolecular Structures Craig Martin and Jeanne Hardy December 9, 2005 The goal of pain management has been sought after for many years, meaning people are constantly striving to improve function, enabling individuals to participate in day-to-day activities. One specific aspect of this field lies within the area inflammation. Various diseases such as rheumatic disease and arthritis cause a great deal of pain due to inflammation. For this reason, the mechanism of this disorder needed to be determined so anti-inflammatory drugs could be developed in order to aid individuals with such a disease. In the 1930’s, the prostaglandin was determined to be a major component in pain and inflammation, allowing the mode of action of pain management to begin to take shape. Prostaglandins were discovered to be mediators in inflammation that can be found in virtually all tissues and organs. “They are autocrine and paracrine lipid mediators which act upon platelet, endothelium, uterine and mast cells among others.” 1 After this became known, the mechanism for these inflammation mediators was determined in order to try to find a way to inhibit the cycle. In doing this a fascinating enzyme was discovered called cyclooxygenase (otherwise known as COX) which would aid in their journey to anti-inflammatory drug discovery due to the fact that this enzyme catalyzes this conversion of arachidonic acid to PGG2, an vital step in the prostaglandin cycle. Now prostaglandins are synthesized in the cell from arachidonic acid. This component is released from membrane phospholipids by phospholipase A2, which is activated by various stimuli. -
Computational Analysis of Cyclooxygenase Inhibition
COMPUTATIONAL ANALYSIS OF CYCLOOXYGENASE INHIBITION: ENERGETICS AND DYNAMICS By Christopher Williams Moth Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Chemistry May, 2008 Nashville, Tennessee Approved: Professor Terry P. Lybrand Professor Lawrence J. Marnett Professor Michael R. Waterman Professor Ned A. Porter Professor Alan R. Brash DEDICATION To my father, Brian, who wished he could have been a chemist. To my wife, Valerie, for encouraging me to pursue my dreams. ii ACKNOWLEDGEMENTS There are no adequate words to convey my sincerest thanks to Dr. Terry Lybrand for inviting me into in his lab, and to Dr. Larry Marnett for allowing me to attend his experimental lab meetings. I deeply appreciate the guidance and patience of my committee, as I navigated the murky waters of biomolecular simulation. The interdisciplinary atmosphere at Vanderbilt has provided a wonderful backdrop for all of my studies. Thanks to Al Beth and the Chemical and Physical Biology (CPB) program for funding a flexible starting point for my Ph.D. Studies. I have enjoyed financial support from the National Institute of Health through Chemistry Biology Interface training grant T32 GM65086-02 and N.I.H. Research grants NS33290 (Lybrand) and CA89450 (Marnett). And, thanks to the Vanderbilt Dept. of Chemistry for allowing me to T.A. and grade courses in order to fund the most recent years of my graduate studies. We are incredibly fortunate at the Structural Biology Center to have excellent computing resources, and support infrastructure. Special thanks to Jarrod Smith, Brandon Valentine, Roy Hoffman, Sabuj Pattanayek, and Holland Griffis for all their help keeping our software current, and our hardware working well. -
Eicosanoids Mediate Manduca Sexta Cellular Response to the Fungal Pathogen Beauveria Bassiana: a Role for the Lipoxygenase Pathway
46 Lord et al. Archives of Insect Biochemistry and Physiology 51:46–54 (2002) Eicosanoids Mediate Manduca sexta Cellular Response to the Fungal Pathogen Beauveria bassiana: A Role for the Lipoxygenase Pathway Jeffrey C. Lord,1* Sheri Anderson,1 and David W. Stanley2 Many studies have documented the involvement of eicosanoids in insect cellular immune responses to bacteria. The use of the fungal pathogen Beauveria bassiana as a nodulation elicitor, with inhibition of phospholipase A2 by dexamethasone, extends the principle to fungi. This study also provides the first evidence of involvement of the lipoxygenase (LOX) pathway rather than the cyclooxygenase (COX) pathway in synthesis of the nodulation mediating eicosanoid(s). The LOX product, 5(S)- hydroperoxyeicosa-6E,8Z,11Z,14Z-tetraenoic acid (5-HPETE), substantially reversed nodulation inhibition caused by dexam- ethasone and the LOX inhibitors, caffeic acid and esculetin. The COX product, prostaglandin H2 (PGH2), did not reverse the nodulation inhibition by dexamethasone or the COX inhibitor, ibuprofen. None of the inhibitors tested had a significant effect on the phagocytosis of B. bassiana blastospores in vitro. Hemocyte phenoloxidase activity was reduced by dexamethasone, esculetin, and the COX inhibitor, indomethacin. The rescue candidates 5-HPETE and PGH2 did not reverse the inhibition. Arch. Insect Biochem. Physiol. 51:46–54, 2002. Published 2002 Wiley-Liss, Inc.† KEYWORDS: eicosanoid; lipoxygenase; Manduca sexta; Beauveria bassiana; nodulation; insect immunity; fungus INTRODUCTION by Stanley-Samuelson, 1994; Stanley and Howard, 1998; Howard and Stanley, 1999; Stanley, 2000). Eicosanoids are oxygenated metabolites of Insect cellular immune responses to microbial arachidonic acid with a broad array of informa- assault are divided into multicellular nodulation tional functions in a diversity of organisms. -
Oxylipin Response to Acute and Chronic Exercise: a Systematic Review
H OH metabolites OH Review Oxylipin Response to Acute and Chronic Exercise: A Systematic Review Étore F. Signini 1,* , David C. Nieman 2 , Claudio D. Silva 1 , Camila A. Sakaguchi 1 and Aparecida M. Catai 1 1 Physical Therapy Department, Federal University of São Carlos, São Carlos, SP 13565-905, Brazil; [email protected] (C.D.S.); [email protected] (C.A.S.); [email protected] (A.M.C.) 2 North Carolina Research Campus, Appalachian State University, Kannapolis, NC 28081, USA; [email protected] * Correspondence: [email protected] Received: 28 May 2020; Accepted: 19 June 2020; Published: 25 June 2020 Abstract: Oxylipins are oxidized compounds of polyunsaturated fatty acids that play important roles in the body. Recently, metabololipidomic-based studies using advanced mass spectrometry have measured the oxylipins generated during acute and chronic physical exercise and described the related physiological effects. The objective of this systematic review was to provide a panel of the primary exercise-related oxylipins and their respective functions in healthy individuals. Searches were performed in five databases (Cochrane, PubMed, Science Direct, Scopus and Web of Science) using combinations of the Medical Subject Headings (MeSH) terms: “Humans”, “Exercise”, “Physical Activity”, “Sports”, “Oxylipins”, and “Lipid Mediators”. An adapted scoring system created in a previous study from our group was used to rate the quality of the studies. Nine studies were included after examining 1749 documents. Seven studies focused on the acute effect of physical exercise while two studies determined the effects of exercise training on the oxylipin profile. Numerous oxylipins are mobilized during intensive and prolonged exercise, with most related to the inflammatory process, immune function, tissue repair, cardiovascular and renal functions, and oxidative stress.