DOCSLIB.ORG

Fragmentación Del Adn Espermático Y Su Relación Con El Metabolismo Peptídico

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Fragmentación Del Adn Espermático Y Su Relación Con El Metabolismo Peptídico Facultad de Medicina y Enfermería Medikuntza eta Erizaintza Fakultatea Departamento de Fisiología Fisiologia Saila TESIS DOCTORAL FRAGMENTACIÓN DEL ADN ESPERMÁTICO Y SU RELACIÓN CON EL METABOLISMO PEPTÍDICO MEMORIA PRESENTADA POR: Mª Victoria Aparicio Prieto DIRIGIDA POR LOS DOCTORES: Luis Casis Saenz Nerea Subirán Ciudad 2018 TESIS DOCTORAL Facultad de Medicina y Enfermería Medikuntza eta Erizaintza Fakultatea Departamento de Fisiología Fisiologia Saila TESIS DOCTORAL FRAGMENTACIÓN DEL ADN ESPERMÁTICO Y SU RELACIÓN CON EL METABOLISMO PEPTÍDICO MEMORIA PRESENTADA POR: Mª Victoria Aparicio Prieto DIRIGIDA POR LOS DOCTORES: LUIS CASIS SAENZ NEREA SUBIRÁN CIUDAD 2018 Mª Victoria Aparicio Prieto 1 (cc)2018 Mª VICTORIA APARICIO PRIETO (cc by-nc 4.0) TESIS DOCTORAL Mª Victoria Aparicio Prieto 12 TESIS DOCTORAL AGRADECIMIENTOS No sólo los conocimientos científicos son importantes, sino que es tan importante tener al lado un gran equipo humano, generoso y entusiasta. Por lo que quiero decir “GRACIAS” a todas estas personas que han compartido conmigo este proyecto. En primer lugar, me gustaría agradecer este estudio al profesor Dr. Luis Casis, mi director, una gran persona no solo en el ámbito profesional y académico sino también en la parte humana. Gracias a él he podido realizar esta investigación. Ha sido mi compañero en los momentos de bloqueo y un buen tutor cuando necesitaba orientación y apoyo científico. Su amistad, ayuda incondicional más allá de lo que su papel como director exige, interés, actitud siempre positiva y dispuesta para que este proyecto avanzara. Mi agradecimiento a la Dra. Olga Ramón que fue mi codirectora de este proyecto hasta su fallecimiento. Mujer emblemática, luchadora incansable, que me dio la oportunidad de no declinar cuando las cosas se veían difíciles, y que a estas alturas de mi vida me animó a llevar a cabo este proyecto. Siempre tuve en ella un apoyo tanto en lo profesional como en lo personal, siempre sabré que está conmigo. Mi agradecimiento a la Dra. Nerea Subirán, por su interés, apoyo y conocimientos, y a todo el personal del departamento de fisiología. Quiero dar las gracias a mi familia, en primer lugar, a mis queridos padres a los cuales he perdido, pero que siempre me han apoyado y me han dado y me siguen dando fuerzas hasta en los momentos más difíciles, estoy segura que se sentirían felices de ver que había conseguido realizar este proyecto. Su mejor herencia ha sido la educación que me han dado con gran esfuerzo, frase que repito frecuentemente a mis tres hijos Gorka, Josu y Mikel a los cuales tengo que agradecer su apoyo, comprensión y ayuda. No quisiera olvidar a mi querida hermana Arantza que siempre me ha animado. Mi agradecimiento a Julio Morales, gracias por tus atenciones y amistad. Gracias, a mis amigos y compañeros que me han animado en este proyecto con su apoyo, y a los que no me han apoyado, también gracias, porque me ha dado fuerzas para continuar. Mª Victoria Aparicio Prieto 13 TESIS DOCTORAL Esta tesis fue posible gracias al apoyo recibido por Biobanco. No quisiera olvidar a nadie, pero pido disculpas si he olvidado sin querer a alguien. Sin vosotros esto no habría sido posible. A todos GRACIAS!!!!! Mª Victoria Aparicio Prieto 14 TESIS DOCTORAL INDICE Mª Victoria Aparicio Prieto 15 TESIS DOCTORAL Mª Victoria Aparicio Prieto 16 TESIS DOCTORAL INDICE I INTRODUCCIÓN 1. PEPTIDASAS ………………………………………………………….23 1.1. Clasificación y Nomenclatura de las Peptidasas ………………24 1.1.1. Las peptidasas como enzimas interconvertidoras de biopéptidos ……………………………………………………………………………25 1.1.2. Catabolismo proteico y acciones intracrinas de las Peptidasas …………………………………………………………………………….28 1.1.3. Otras acciones de las peptidasas …………………………………28 1.1.4. Las peptidasas en la fisiología y en la patología ...........………29 1.2. Papel de las peptidasas en la fertilidad ………………………….30 1.2.1. Regulación del ciclo sexual: modelo de liberación gonadotrópica ………………………………………………………………………..31 1.2.2. Sistemas de comunicación celular y fertilidad …………………33 2. CARACTERÍSTICAS MOLECULARES DE LAS AMINOPEPTIDASAS ESTUDIADAS ………………………………………...…….35 2.1. Endopeptidasa Neutra (NEP, CD10) (E.C.3.424.11) ...................35 2.2. Aminopeptidasa neutra (APN, CD13) (EC 3.4.11.2) …………….36 2.3. Aminopeptidasa sensible a puromicina (PSA) (EC 3.4.11.14) …………………………………………………………………………41 2.4. Aminopeptidasa B (APB) (EC 3.4.11.6) ……………….………….42 2.5. Dipeptidil Peptidasa IV (DPPIV) (EC 3.4.14.5.) ………………….43 2.6. Cistil aminopeptidasa (Cys-AP) (EC 2.4.11.3) …………………..46 2.7. Aspartil aminopeptidasa (Asp-AP) (EC 3.4.11.21) ……...………47 2.8. Glutamil aminopeptidasa (Glu-AP, APA) (EC 3.4.11.7) ………..48 2.9. Prolil endopeptidasa (PEP) (EC 3.4.21.26) ………………...…….50 3. SISTEMA OPIOIDE ……………………………………...……………52 3.1. Características de los receptores opioides ……………………..52 3.2. Sistema opioide endógeno …………………………………………55 3.3. Activación de los receptores de opioides ……………………….58 3.4. Señalización mediada por receptores de opioides …………….59 3.5. Biosíntesis, transporte, depósito, liberación y metabolismo de los péptidos opioides ……………………………………………………...………..60 Mª Victoria Aparicio Prieto 17 TESIS DOCTORAL 3.6. Acciones fisiológicas de los receptores de opioides …………60 3.7. Implicación del Sistema Opioide en la fertilidad masculina ….61 3.7.1. Control de las hormonas reproductoras mediante los opioides ………………………………………………………………………………..61 3.7.2. Control de la función testicular por los opioides ………………63 3.7.3. Control de la función espermática por los opioides …………..68 3.8. Regulación de la fertilidad femenina (opioides/aminopeptidasas) ……………………………………………………….70 4. SISTEMA RENINA-ANGIOTENSINA (SRA) ………………………74 4.1. Sistema renina angiotensina (SRA): de su concepto clásico o sistémico al descubrimiento de SRA local o tisular …………………………..74 4.2. SRA intracelular ………………………………………………………77 4.3. Ejes o vías que componen el SRA ………………………………..77 4.4. Componentes de SRA ……………………………………………….79 4.4.1. Angiotensinógeno y angiotensinas ……………………………....79 4.5. Receptores ……………………………………..……………………..80 4.6. El SRA en la fertilidad masculina …………………………………83 4.6.1. El SRA y su implicación en la función testicular ………………83 4.6.2. El SRA y su implicación en la función espermática …………..85 5. ESPERMATOGÉNESIS ……………………………………………...88 5.1. Espermatocitogénesis ………………………………………………89 5.2. Espermiogénesis…………………………………………..…………90 5.3. Regulación Endocrina y Paracrina de la Espermatogénesis ..92 6. ESTRUCTURA DE LOS ESPERMATOZOIDES ………………….93 7. FRAGMENTACIÓN DEL ADN ESPERMÁTICO ………………….97 7.1. Mecanismos por los que se produce la fragmentación del ADN …………………………………………………………………………………...100 7.1.1. Inducción de la apoptosis durante el proceso de la espermatogénesis …………………………………………………….….100 7.1.2. Rotura del ADN durante el proceso de espermiogénesis …..102 7.1.3. Fragmentación del ADN espermático post-testicular ………..103 7.1.4. Activación de Caspasas y Endonucleasas …………………….108 7.1.5. Daño del ADN inducido por la radioterapia y quimioterapia .110 7.1.6. Daño del ADN inducido por sustancias tóxicas ambientales.110 Mª Victoria Aparicio Prieto 18 TESIS DOCTORAL II OBJETIVOS ………………………………………………………………..113 III MATERIAL Y MÉTODOS ………………………………………………..117 1. Consentimientos y autorizaciones ………………………………117 1.1. Comite ética Universidad ………………………………………….118 1.2. Comite ética Cruces ………………………………………………..120 1.3. Carta Dra. Ramón ……………………………………………..……121 1.4. Consentimiento Dr. Matorras …………………………………….122 1.5. Hoja informativa …………………………………………………….124 1.6. Autorización …………………………………………………………126 2. Aspectos clínicos …………………………………………………..127 2.1. Inclusión ……………………………………………………………..127 2.2. Estimulación ovárica ………………………………………………127 2.3. Recogida de las muestras seminales …………………………..128 2.4. Preparación de las muestras seminales para uso clínico …..128 2.4.1. Evaluación de la muestra …………………………………………128 2.4.2. Preparación de la muestra ………………………………………..129 2.4.3. Análisis de la movilidad espermática …………………………..130 2.5. Inseminación Intrauterina …………………………………………133 2.6. Fase lutea …………………………………………………………….133 2.7. Definición de embarazo ……………………………………………133 2.8. Procesamiento de las muestras para el estudio ……………...133 2.8.1. Protocolo congelación …………………………………………….134 2.8.2. Protocolo descongelación ………………………………………..134 3. Fragmentación del ADN espermático …………………………..134 4. Columnas de Anexina ……………………………………………..137 5. Actividad enzimática ……………………………………………….139 5.1. Actividad enzimática por espectrofluorimetría .......................139 5.1.1. Análisis de la actividad por ensayos enzimáticos ……………143 5.1.2. Determinación de la actividad de las aminopeptidasas ……..144 5.1.3. Fundamento general ……………………………………………….145 5.1.4. Fundamento particular para cada enzima ……………………..146 5.1.5. Análisis de datos de las actividades peptidásicas …………..148 5.1.6. Técnica para la cuantificación de proteínas …………………..148 5.2. Actividad enzimática por citometría de flujo ………………….149 Mª Victoria Aparicio Prieto 19 TESIS DOCTORAL 5.2.1. Fundamento …………………………………………………………149 5.2.2. Preparación de las muestras (Citometría semi-cuantitativa).150 6. Receptores …………………………………………………………..153 6.1. Receptores sistema renina angiotensina. Inmunocitoquímica ………………………………………………………………...155 6.2. Receptores opioides. Inmunocitoquímica ……………………..156 IV RESULTADOS ……………………………………………………………159 1. Aspectos clínicos ………………………………………………….159 2. Resultados actividad enzimática ………………………………..163 2.1. Actividad enzimática por espectrofluorimetria ……………….163 2.2. Actividad enzimática por citometria de flujo ………………….171 3. Receptores …………………………………………………………..173
Load more

Recommended publications
  • Formylpeptide Receptor N Antagonist at The
    The Endogenous Opioid Spinorphin Blocks fMet-Leu-Phe-Induced Neutrophil Chemotaxis by Acting as a Specific Antagonist at the N-Formylpeptide Receptor This information is current as Subtype FPR of October 1, 2021. Thomas S. Liang, Ji-Liang Gao, Omid Fatemi, Mark Lavigne, Thomas L. Leto and Philip M. Murphy J Immunol 2001; 167:6609-6614; ; doi: 10.4049/jimmunol.167.11.6609 Downloaded from http://www.jimmunol.org/content/167/11/6609 References This article cites 48 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/167/11/6609.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Endogenous Opioid Spinorphin Blocks fMet-Leu-Phe-Induced Neutrophil Chemotaxis by Acting as a Specific Antagonist at the N-Formylpeptide Receptor Subtype FPR Thomas S.
    [Show full text]
  • Opioid Peptides 49 Ryszard Przewlocki
    Opioid Peptides 49 Ryszard Przewlocki Abbreviations ACTH Adrenocorticotropic hormone CCK Cholecystokinin CPA Conditioned place aversion CPP Conditioned place preference CRE cAMP response element CREB cAMP response element binding CRF Corticotrophin-releasing factor CSF Cerebrospinal fluid CTAP D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (m-opioid receptor antagonist) DA Dopamine DOP d-opioid peptide EOPs Endogenous opioid peptides ERK Extracellular signal-regulated kinase FSH Follicle-stimulating hormone GnRH Gonadotrophin-releasing hormone HPA axis Hypothalamo-pituitary-adrenal axis KO Knockout KOP k-opioid peptide LH Luteinizing hormone MAPK Mitogen-activated protein kinase MOP m-opioid peptide NOP Nociceptin opioid peptide NTS Nucleus tractus solitarii PAG Periaqueductal gray R. Przewlocki Department of Molecular Neuropharmacology, Institute of Pharmacology, PAS, Krakow, Poland Department of Neurobiology and Neuropsychology, Jagiellonian University, Krakow, Poland e-mail: [email protected] D.W. Pfaff (ed.), Neuroscience in the 21st Century, 1525 DOI 10.1007/978-1-4614-1997-6_54, # Springer Science+Business Media, LLC 2013 1526 R. Przewlocki PDYN Prodynorphin PENK Proenkephalin PNOC Pronociceptin POMC Proopiomelanocortin PTSD Posttraumatic stress disorder PVN Paraventricular nucleus SIA Stress-induced analgesia VTA Ventral tegmental area Brief History of Opioid Peptides and Their Receptors Man has used opium extract from poppy seeds for centuries for both pain relief and recreation. At the beginning of the nineteenth century, Serturmer first isolated the active ingredient of opium and named it morphine after Morpheus, the Greek god of dreams. Fifty years later, morphine was introduced for the treatment of postoper- ative and chronic pain. Like opium, however, morphine was found to be an addictive drug.
    [Show full text]
  • Opioids, Neutral Endopeptidase, Its Inhibitors and Cancer: Is There a Relationship Among Them?
    Arch. Immunol. Ther. Exp. DOI 10.1007/s00005-014-0311-0 REVIEW ARTICLE Opioids, Neutral Endopeptidase, its Inhibitors and Cancer: Is There a Relationship among them? Magdalena Mizerska-Dudka • Martyna Kandefer-Szerszen´ Received: 11 March 2014 / Accepted: 18 June 2014 Ó The Author(s) 2014. This article is published with open access at Springerlink.com Abstract The role of endogenous animal opioids in the CKI Cyclin dependent inhibitory kinases biology of cancer is widely recognized but poorly under- ECM Extracellular matrix stood. This is, among others, because of the short half-life FAK Focal adhesion kinase of these peptides, which are quickly inactivated by endo- GPI-complex Glycosyl phosphatidyl inositol complex peptidases, e.g., neutral endopeptidase (NEP, CD10). It has MAP kinases Mitogen-activated protein kinases been established that NEP is engaged in the modulation of mRNA Messenger RNA the tumor microenvironment, among others that of colon NEP Neutral endopeptidase cancer, by exerting influence on cell growth factors, the NK Natural killer cells extracellular matrix and other biologically active sub- OGF Opioid growth factor stances. Although there are some discrepancies among the OGFr Opioid growth factor receptor findings on the role of both opioids and NEP in cancer PROL1 Proline rich, lacrimal 1 development, authors agree that their role seems to depend PTEN Phosphatase and tensin homolog deleted on the origin, stage and grade of tumor, and even on the on chromosome Ten method of examination. Moreover, recently, natural SGP-T Submandibular gland peptide-T inhibitors of NEP, such as sialorphin, opiorphin and spin- SMR1 Submandibular rat1 protein orphin have been detected.
    [Show full text]
  • List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify
    List of Psychoactive Drug Spirits for MD A-Methylfentanyl, Abilify, abnormal basal ganglia function, abuse of medicines, Aceperone, Acepromazine, Aceprometazine, Acetildenafil, Aceto phenazine, Acetoxy Dipt, Acetyl morphone, Acetyl propionyl morphine, Acetyl psilocin, Activation syndrome, acute anxiety, acute hypertension, acute panic attacks, Adderall, Addictions to drugs, Addictions to medicines, Addictions to substances, Adrenorphin, Adverse effects of psychoactive drugs, adverse reactions to medicines, aggression, aggressive, aggressiveness, agitated depression, Agitation and restlessness, Aildenafil, Akuammine, alcohol abuse, alcohol addiction, alcohol withdrawl, alcohol-related brain damage, alcohol- related liver damage, alcohol mix with medicines for adverse reaction, Alcoholism, Alfetamine, Alimemazine, Alizapride, Alkyl nitrites, allergic breathing reactions to meds, choking to anaphallectic shock, & death; allergic skin reactions to meds, rash, itchyness, hives, welts, etc, Alletorphine, Almorexant, Alnespirone, Alpha Ethyltryptamine, Alpha Neoendorphin, alterations in brain hormones, alterations in mental status, altered consciousness, altered mind, Altoqualine, Alvimopan, Ambien, Amidephrine, Amidorphin, Amiflamine, Amisulpride, Amphetamines, Amyl nitrite, Anafranil, Analeptic, Anastrozole, Anazocine, Anilopam, Antabuse, anti anxiety meds, anti dopaminergic activity, anti seizure meds, Anti convulsants, Anti depressants, Anti emetics, Anti histamines, anti manic meds, anti parkinsonics, Anti psychotics, Anxiety disorders,
    [Show full text]
  • Molecular Insights Into the Interaction of Hemorphin and Its Targets
    www.nature.com/scientificreports OPEN Molecular insights into the interaction of hemorphin and its targets Received: 21 January 2019 Amanat Ali1, Bincy Baby1, Soja Saghar Soman2 & Ranjit Vijayan1 Accepted: 17 September 2019 Hemorphins are atypical endogenous opioid peptides produced by the cleavage of hemoglobin beta Published: xx xx xxxx chain. Several studies have reported the therapeutic potential of hemorphin in memory enhancement, blood regulation, and analgesia. However, the mode of interaction of hemorphin with its target remains largely elusive. The decapeptide LVV-hemorphin-7 is the most stable form of hemorphin. It binds with high afnity to mu-opioid receptors (MOR), angiotensin-converting enzyme (ACE) and insulin-regulated aminopeptidase (IRAP). In this study, computational methods were used extensively to elucidate the most likely binding pose of mammalian LVV-hemorphin-7 with the aforementioned proteins and to calculate the binding afnity. Additionally, alignment of mammalian hemorphin sequences showed that the hemorphin sequence of the camel harbors a variation – a Q > R substitution at position 8. This study also investigated the binding afnity and the interaction mechanism of camel LVV-hemorphin-7 with these proteins. To gain a better understanding of the dynamics of the molecular interactions between the selected targets and hemorphin peptides, 100 ns molecular dynamics simulations of the best-ranked poses were performed. Simulations highlighted major interactions between the peptides and key residues in the binding site of the proteins. Interestingly, camel hemorphin had a higher binding afnity and showed more interactions with all three proteins when compared to the canonical mammalian LVV-hemorphin-7. Thus, camel LVV-hemorphin-7 could be explored as a potent therapeutic agent for memory loss, hypertension, and analgesia.
    [Show full text]
  • Opioid Receptor
    Opioid Receptor Opioid receptors are a group of G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. Opioid receptors are distributed widely in the brain, and are found in the spinal cord and digestive tract. Opioid receptors are molecules, or sites, within the body that are activated by opioid substances. Opioid receptors inhibit the transmission of impulse in excitatory pathways within the human body system. These pathways include the serotonin, catecholamine, and substance P pathways, which are all implicated in pain perception and feelings of well-being. Opioid receptors are further subclassified into mu, delta, and kappa receptors. All the classes, while exhibiting differing modes of action, share some basic similarities. They all are driven by the potassium pump mechanism, which is found on the plasma membrane of the majority of cells. www.MedChemExpress.com 1 Opioid Receptor Agonists, Antagonists, Inhibitors, Activators & Modulators 6'-GNTI dihydrochloride 6-Alpha Naloxol Cat. No.: HY-110302 (Alpha-Naloxol) Cat. No.: HY-12799 6'-GNTI dihydrochloride, a κ-opioid receptor (KOR) 6-Alpha Naloxol(Alpha-Naloxol) is an opioid agonist, displays bias toward the activation of G antagonist closely related to naloxone; a human protein-mediated signaling over β-arrestin2 metabolite of naloxone. recruitment. 6'-GNTI 6'-GNTI dihydrochloride only activates the Akt pathway in striatal neurons. Purity: >98% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 1 mg, 5 mg Size: 1 mg, 5 mg 6-beta-Naloxol D5 hydrochloride Ac-RYYRIK-NH2 (6β-Naloxol D5 hydrochloride) Cat. No.: HY-12780S Cat.
    [Show full text]
  • Quality Control Record Opioid Peptide Library
    Quality Control Record Opioid Peptide Library Catalog No. L‐002 Well # Position* Catalog # Product Name M.W. PLATE I 1I‐A‐2 021‐01 Dynorphin, big (Human, Rat, Mouse, Porcine) 3982.26 2I‐A‐3 021‐03 Dynorphin A (Human, Rat, Mouse, Porcine) 2147.51 3I‐A‐4 021‐08 Dynorphin A (1‐6) / Endorphin (1‐6), alpha‐Neo / Leu‐Enkephalin‐Arg (Human, Rat, Mouse, Porcine) 711.38 4I‐A‐5 021‐21 Dynorphin A (1‐13) (Human, Rat, Mouse, Porcine) 1602.99 5I‐A‐6 021‐24 Dynorphin A (2‐13) amide (Human, Rat, Mouse, Porcine) 1439.82 6I‐A‐7 021‐30 Dynorphin A (2‐17) (Human, Rat, Mouse, Porcine) 1983.14 7I‐A‐8 021‐37 Dynorphin B / Rimorphin (Human, Rat, Mouse, Porcine) 1570.86 8I‐A‐9 021‐40 Endorphin, alpha‐Neo (Porcine) 1228.46 9I‐A‐10 021‐44 Endorphin, beta‐neo 1099.59 10 I‐A‐11 021‐55 Orphanin FQ / Nociceptin (Human, Rat, Mouse, Ox) 1809.06 11 I‐B‐2 021‐58 pro‐Orphanin FQ (85‐119) / pro‐Nociceptin (85‐119) / Nocistatin‐35 (Rat) 3907.25 12 I‐B‐3 021‐59 pro‐Orphanin FQ (141‐157) / pro‐Nociceptin (141‐157) 2081.4 13 I‐B‐4 021‐70 [Phe‐psi‐Gly]‐Orphanin FQ (1‐13) amide / [Phe‐psi‐Gly]‐Nociceptin (1‐13) amide (Human, Rat, Mouse, Ox) 1376.6 14 I‐B‐5 021‐71 Orphanin FQ (1‐13) amide / Nociceptin (1‐13) amide (Human, Rat, Mouse, Ox) 1381.6 15 I‐B‐6 021‐75 prepro‐Orphanin FQ (111‐127) / Nocistatin / PNP‐3 (Bovine) 1927.1 16 I‐B‐7 021‐78 prepro‐Orphanin FQ (98‐127) / Nocistatin‐30 (Human) 3561.98 17 I‐B‐8 021‐80 PNP‐3‐8P (Bovine) 1015.13 18 I‐B‐9 021‐81 PNP‐2/3 / Nocistatin‐41 (Mouse) 4375.71 19 I‐B‐10 021‐85 prepro‐Orphanin FQ (154‐181), free acid (Rat) / prepro‐Orphanin FQ
    [Show full text]
  • Neuropeptidases, Stress, and Memory—A Promising Perspective
    AIMS Neuroscience, 3 (4): 487–501. DOI: 10.3934/Neuroscience.2016.4.487 Received 18 October 2016, Accepted 6 December 2016, Published 16 December 2016 http://www.aimspress.com/journal/neuroscience Review article Neuropeptidases, Stress, and Memory—A Promising Perspective I. Prieto 1, A.B. Segarra 1, M. de Gasparo 2, and M. Ramírez-Sánchez 1, * 1 Unit of Physiology, University of Jaén, Jaén, Spain; 2 Cardiovascular and Metabolic Syndrome Advisor, Rossemaison, Switzerland * Correspondence: Email: [email protected]; Tel: 34-953-212302 Abstract: Stress has been demonstrated to be a key modulator in learning and memory processes, in which the hippocampus plays a central role. A great number of neuropeptides have been reported to modulate learning and memory under stressful conditions. Neuropeptidases are proteolytic enzymes capable of regulating the function of neuropeptides in the central and peripheral nervous system. In this regard, a number of neuropeptidases, i.e. angiotensinases, oxytocinase, or enkephalinases, have received attention. Their involvement in stress and memory processes is a promising perspective, as it is possible to influence their activities through various activators or inhibitors and, consequently, to pharmacologically modulate the functions of the endogenous substrates that are involved. The present review describes the key findings showing the involvement of neuropeptides and neuropeptidases in stress and memory and highlights the role of the hippocampus in these processes. Keywords: stress; memory; hippocampus; aminopeptidases; angiotensins; oxytocin; vasopressin; enkephalins 1. Stress and Memory In order to increase the chances of survival under stressful conditions, the body coordinately responds to maintain homeostasis (i.e. the internal environment stability) despite changes in the external surrounding [1].
    [Show full text]
  • Explorative Screening of Bioactivities Generated by Plant-Based Proteins After in Vitro Static Gastrointestinal Digestion
    nutrients Article Explorative Screening of Bioactivities Generated by Plant-Based Proteins after In Vitro Static Gastrointestinal Digestion Camille Dugardin 1, Benoit Cudennec 1,* ,Mélissa Tourret 1, Juliette Caron 2, Laetitia Guérin-Deremaux 2, Josette Behra-Miellet 1, Catherine Lefranc-Millot 3 and Rozenn Ravallec 1,* 1 UMR-T 1158, BioEcoAgro, University of Lille, F-59000 Lille, France; [email protected] (C.D.); [email protected] (M.T.); [email protected] (J.B.-M.) 2 Nutrition and Health Research & Development, Roquette, F-62136 Lestrem, France; [email protected] (J.C.); [email protected] (L.G.-D.) 3 Nutrition and Health Research & Development, Roquette, F-59110 La Madeleine, France; [email protected] * Correspondence: [email protected] (B.C.); [email protected] (R.R.) Received: 13 October 2020; Accepted: 2 December 2020; Published: 5 December 2020 Abstract: The gastrointestinal digestion of food proteins can generate peptides with a wide range of biological activities. In this study, we screened various potential bioactivities generated by plant-based proteins. Whey protein as an animal protein reference, five grades of pea protein, two grades of wheat protein, and potato, fava bean, and oat proteins were submitted to in vitro SGID. They were then tested in vitro for several bioactivities including measures on: (1) energy homeostasis through their ability to modulate intestinal hormone secretion, to inhibit DPP-IV activity, and to interact with opioid receptors; (2) anti-hypertensive properties through their ability to inhibit ACE activity; (3) anti-inflammatory properties in Caco-2 cells; (4) antioxidant properties through their ability to inhibit production of reactive oxygen species (ROS).
    [Show full text]
  • Swepep, a Database Designed for Endogenous Peptides and Mass Spectrometry*
    Research SwePep, a Database Designed for Endogenous Peptides and Mass Spectrometry* Maria Fa¨ lth‡§, Karl Sko¨ ld‡§, Mathias Norrman‡, Marcus Svensson‡§, David Fenyo¨ ʈ, and Per E. Andren‡§** A new database, SwePep, specifically designed for en- ular biological approaches in its ability to characterize the dogenous peptides, has been constructed to significantly processing of functional gene products. It allows direct ob- speed up the identification process from complex tissue servation of changes in the amount of peptides and small samples utilizing mass spectrometry. In the identification proteins and their post-translational modifications. The main process the experimental peptide masses are compared difficulties in the analysis of endogenous peptides are their with the peptide masses stored in the database both with rapid degradation during extraction and purification (4) and Downloaded from and without possible post-translational modifications. that their average tissue content is less than 0.1% of that of This intermediate identification step is fast and singles out proteins (5). Endogenous peptides also often contain post- peptides that are potential endogenous peptides and can 1 later be confirmed with tandem mass spectrometry data. translational modifications (PTMs) (e.g. acetylation, amida- Successful applications of this methodology are pre- tion, and phosphorylation), adding to the difficulty of deci- sented. The SwePep database is a relational database phering the obtained mass spectra. www.mcponline.org developed using MySql and Java. The database contains An important functional group of the peptidome is the en- 4180 annotated endogenous peptides from different tis- dogenous peptides in the brain. The neuropeptides range in sues originating from 394 different species as well as 50 length from 3 to 100 amino residues and are up to 50 times novel peptides from brain tissue identified in our labora- larger than classical neurotransmitters (6).
    [Show full text]
  • Structure-Activity Study of Lvv-Hemorphin-7
    JPET Fast Forward. Published on November 25, 2002 as DOI: 10.1124/jpet.102.045492 JPET FastThis Forward. article has not Published been copyedited on andNovember formatted. The 25, final 2002 version as mayDOI:10.1124/jpet.102.045492 differ from this version. 26 JPET/2002/45492 STRUCTURE-ACTIVITY STUDY OF LVV-HEMORPHIN-7: ANGIOTENSIN AT4 RECEPTOR LIGAND AND INHIBITOR OF INSULIN-REGULATED AMINOPEPTIDASE (IRAP) Joohyung Lee*, Tomris Mustafa*, Sharon G. McDowall, Frederick A.O. Mendelsohn, Michelle Brennan, Rebecca A. Lew, Anthony L Albiston, and Siew Yeen Chai. Downloaded from jpet.aspetjournals.org Howard Florey Institute (J.l., T.M., S.G.M., F.A.O.M. M.B. A.L.A. and S.Y.C.) and at ASPET Journals on September 29, 2021 Department of Pharmacology (J.L.), University of Melbourne, Parkville, Victoria, 3010, Australia and Baker Heart Research Institute, Melbourne, Victoria 8008, Australia (R.A.L.) 1 Copyright 2002 by the American Society for Pharmacology and Experimental Therapeutics. JPET Fast Forward. Published on November 25, 2002 as DOI: 10.1124/jpet.102.045492 This article has not been copyedited and formatted. The final version may differ from this version. 26 JPET/2002/45492 Running title: Structure-activity study of LVV-hemorphin-7 Address correspondence: Dr Siew Yeen Chai Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, 3010, Australia Tel: +61 3 8344 7332 Fax: +61 3 9348 1707 Downloaded from Email: [email protected] jpet.aspetjournals.org Number of text pages: 21 Number of tables: 4 Number of figures: 3 at ASPET Journals on September 29, 2021 Number of references: 23 Number of words (Abstract): 238 words Number of words (Introduction): 708 words Number of words (Discussion): 1100 words Recommended Section: Endocrinology and Reproduction Abbreviations: Ang IV, angiotensin IV; IRAP, Insulin-regulated aminopepitdase; Leu-β-Na, Leu-β-naphthylamide.
    [Show full text]
  • Sex Differences in Opioid-Mediated Effects: Role Of
    Sex Differences in Opioid-Mediated Effects: Role of Androgens Jessica Sharp1, Tallia Pearson1, and Mark Smith1 1Davidson College October 2, 2020 Abstract An abundance of data indicate there are sex differences in endogenous opioid peptides and opioid receptors, leading to functional differences in sensitivity to opioid-mediated behaviors between males and females. Many of these sex differences are mediated by the effects of gonadal hormones on the endogenous opioid system. Whereas much research has examined the role of ovarian hormones on opioid-mediated endpoints, comparatively less research has examined the role of androgens. This review describes what is currently known regarding the influence of androgens on opioid-mediated endpoints and how androgens may contribute to sex differences in opioid-mediated effects. The review also addresses the clinical implications of androgenic modulation of opioid-mediated behaviors and suggests future lines of research for preclinical and clinical investigators, We conclude that further investigation into androgenic modulation of opioid-mediated effects may lead to new options for addressing conditions such as chronic pain and substance use disorders. 1. Introduction A large body of literature reveals significant sex and gender differences in opioid-mediated effects. Many of these differences are clinically meaningful and have public health implications. For instance, sex differences in sensitivity to opioid-mediated analgesia contribute to significant differences in the potency and efficacy of opioid analgesics between men and women treated for acute and chronic pain (Craft, 2008; Neisters et al., 2010; Loyd & Murphy, 2014; Lee & Ho, 2013). Similarly, sex differences in opioid-mediated reward contributes to differences in the risk of developing an opioid use disorder in men and women prescribed opioids or using opioids recreationally (Lopresti et al, 2020; Kokane & Perotti, 2020; Becker & Chartoff, 2019).
    [Show full text]