UO PHARMACOLOGY

This Operative Unit ( OU) focus on Cellular Pharmacology and Experimental Pharmacology and Toxicology

Responable (RUO)
Prof. Franco Bernini
Dipartimento di Farmacia
Viale delle Scienze 27/a - 43124 Parma
e-mail: fbernini@unipr.it
CV

Competences

(Prof. Bernini) The Laboratory of Cellular Pharmacology provides expertise related to the study of cellular processes involved in atherosclerosis. The most significant projects concern the study of the mechanisms that regulate lipid metabolism and their pharmacological modulation, with particular attention to the evaluation of the functionality of HDL and reverse cholesterol transport. These studies are conducted both in cellular models in vitro and in experimental models in vivo.

(Prof.ssa Barocelli) This group focus on Experimental Pharmacology and Toxicology, pharmacological, toxicological and pharmacokinetic studies in rodents with specific expertise on issues related to the gastrointestinal tract, hemostasis, with inflammatory / algesic, such behavioral changes. Besides the availability of in vivo experimental models are investigated the mechanisms of action in tissues, cells and cell culture.

More information:
Prof. Franco Bernini - In particular lines of research can be divided into three main topics:

  • In vitro studies on the intracellular metabolism of cholesterol.
    The research is to study the processes that regulate the intracellular content of cholesterol in murine macrophages and human rights, including the uptake and efflux of cholesterol through the 4 main mechanisms: 1) the aqueous diffusion (AD), 2) the 'efflux mediated by scavenger receptor class B type I (SR-BI), and 3) the efflux mediated by' ATP-binding cassette transporter A1 (ABCA1), 4) the efflux mediated by 'ATP-binding cassette transporter G1 ( ABCG1). Other aspects of the study of cellular metabolism of cholesterol on the evaluation of the activity 'esterifying enzyme acyl-coenzyme A-cholesterol acyltransferase (ACAT) activity hydrolyzing cholesterol by the enzyme cholesterol ester hydrolase (NCEH), the intracellular regulation the synthesis of cholesterol, free cholesterol levels of the plasma membrane and the consequent changes in morphological and functional cell membranes.
  • Studies in experimental models in vivo for the evaluation of reverse cholesterol transport (RCT). this group has contributed to the development of a method for quantifying the RCT in vivo, the physiological process by which cholesterol is transported by macrophages to the liver for subsequent elimination from the body. The novelty of this approach is to measure the transport which occurs specifically from the macrophage, which is the main pool involved in atherogenesis, and not as previously by extrahepatic tissues in general. Therefore, the estimate dell'RCT involving the cholesterol by macrophages is of particular importance in order to identify nutritional or pharmacological strategies with potential anti-atherosclerotic activity.
  • Ex vivo studies on the ability of the human or animal serum to promote cholesterol efflux, which is a parameter of the functionality of HDL. The efficiency of the reverse cholesterol transport in humans can be estimated by the ability of serum to promote the efflux of cellular cholesterol, the first and rate-limiting step in this process. In particular, the composition of HDL subfraction influence both the mechanism and the efficiency lipid efflux. The study of the efficiency of serum in promoting efflux can potentially be a valid method for the prediction of cardiovascular risk, since the measurement of the function of HDL, represented by the ability to promote the efflux, the more of their circulating concentration, can be associated with the development of atherosclerotic plaques. The efficiency of the serum in promoting the efflux of cholesterol depends on the capacity of HDL subfractions to interact with specific receptors or transporters involved nell'efflusso and to act as acceptors of extracellular cholesterol. This group has a proven track record in assessing the ability of serum to promote cholesterol efflux through the use of different cell models and experimental conditions that allow you to estimate the contribution of the different efflux mechanisms.

  • Prof.ssa Elisabetta Barocelli
    This group has expertise in the following areas:

    1. In vivo, ex vivo and in vitro functional alterations associated with the local and remote inflammatory states induced by ischemia / reperfusion mesenteric conditions of intestinal stenosis and in experimental colitis. This investigation involves the determination of tissue and plasma biochemical markers, morphological, immunohistochemical and mechanical responses of intestinal smooth muscle preparations and the evaluation of their pharmacological modulation of base or by exposure to functional foods.
    2. Study of modulation of gastric secretory processes and the integrity of the gastric mucosal barrier in experimental models of gastro-duodenal ulcers induced acid produced by NSAIDs or ethanol in rodents. Evaluation of the gastric secretory component and markers of mucosal cytoprotection in vivo and in vitro.
    3. In vivo study of the analgesic and anti-inflammatory properties of natural products and synthetic and their mechanisms of action, including an evaluation of the relationship between effective doses and tolerated doses (gastro effects, sedative effects) and determination of the underlying mechanisms through targeted testing in vitro.
    4. Study of the effects resulting from nutritional and protective subacute and chronic administration of complex foods, their components, dietary supplements and functional foods in rodents maintained under physiological conditions or subjected to dietary change. Study in rodents of subchronic toxicological effects of food contaminants generated during production processes.
    5. In vivo and ex vivo pharmacological modulation of platelet aggregation by new thrombolytic agents / antithrombotic and definition of tolerability and handling.
    6. Development of ligands of the Eph-ephrin system as potential chemotherapeutic drugs through a molecular target in vitro (binding studies in cell-free systems and functional studies of proliferation, migration and angiogenesis in cell lines) and in vivo (xenograft in mice).

    COLLABORAZIONI NAZIONALI:
    Prof. Franceschini G. e Prof.ssa Calabresi L., Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano.
    Prof. Corsini, Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano.
    Prof. Calandra S., Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia
    Prof. Arca M., Dipartimento di Clinica e Terapia Medica, I Facoltà di Medicina e Chirurgia, “Sapienza” Università di Roma.
    Prof. Vigna G., Dipartimento di Medicina Clininca e Sperimentale, Università di Ferrara
    Prof. Bertolini S, U.O. di Medicina Interna e Prevenzione delle Vasculopatie, Dipartimento di Medicina Interna, Università di Genova.
    Prof. Sampietro T., CNR Istituto di Fisiologia Clinica, Pisa, Italy.
    Prof. Zavaroni I., Dipartimento di Medicina Interna e Scienze Biomediche, Azienda Ospedaliero-Universitaria di Parma
    Prof. Borghi C., Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche
    Università degli Studi di Bologna
    Prof. Lupattelli G., Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia
    Prof. Meroni P.L., Divisione di Reumatologia, Istituto G Pini, Università degli Studi di Milano.
    Blandizzi Corrado, Prof. Ordinario di Farmacologia presso il Dipartimento di Medicina Interna - Università di Pisa; Divisione di Farmacologia e Chemioterapia - via Roma, 55 56126 Pisa
    Calderone Vincenzo, Ricercatore di Farmacologia presso il Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie – Università di Pisa; Via Bonanno 6 56126 Pisa
    De Amici Marco, Professore Ordinario di Chimica Farmaceutica presso il Dipartimento di Scienze Farmaceutiche "Pietro Pratesi" – Università di Milano; Via L. Mangiagalli 25 - 20133 Milano
    Bruno Olga, Professore Ordinario di Chimica Farmaceutica presso il Dipartimento di Scienze Farmaceutiche – Università di Genova; Viale Benedetto XV, 3 16132 Genova
    Quaglia Wilma, Professore Associato di Chimica Farmaceutica presso Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino; Via S. Agostino 1, 62032 Camerino
    Di Braccio Mario, Professore Associato di Chimica Farmaceutica presso il Dipartimento di Scienze Farmaceutiche – Università di Genova; Viale Benedetto XV, 3 16132 Genova
    Blandini Fabio, Centro di Ricerca Interdipartimentale per la malattia di Parkinson– Fondazione "Istituto Neurologico Nazionale C. Mondino" IRCCS; Via Mondino, 2 27100 Pavia
    Petronini Piergiorgio, Professore Ordinario di Patologia presso la Sezione di Oncologia Sperimentale del Dipartimento di Medicina Sperimentale – Università di Parma; Via Volturno, 39, 43125 Parma
    Mutti Antonio,Professore Ordinario di Medicina del lavoro presso la Sezione di Medicina del Lavoro del Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione – Università di Parma; Via Gramsci, 14, 43125 Parma

    COLLABORAZIONI INTERNAZIONALI:
    Rothblat George H., Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA USA
    John Chapman, Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S551, Paris, France.
    Rudel LL, Department of Lipid Science, Wake Forest University School of Medicine, Winston-Salem, NC USA
    Parini P., Departments of Laboratory Medicine, Biosciences and Nutrition, Medicine, and Surgery, Karolinska Institutet, Stockholm, Sweden
    Jessup Wendy, Centre for Vascular Research, University of New South Wales, Sydney NSW 2052, Australia
    Kempen HJ., F. Hoffmann-La Roche AG, Pharma Preclinical Research, Basel, Switzerland
    Van Eck M. Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
    Sternini Catia MD Professor, Departments of Medicine and Neurobiology, David Geffen School of Medicine at UCLA Los Angeles, CA 90073
    Mohr Klaus MD. Pharmazeutisches Institut, Pharmakologie und Toxikologie Gerhard-Domagk-Str. 3, D-53347 Bonn
    Perretti Mauro PhD Professor William Harvey Research Limited John Vane Science CentreCharterhouse Square LONDON EC1M 6BQ UK
    Vergnolle Nathalie PhD Professor INSERM U 563 CHU Purpan, BP 3028 31024 Toulouse Cedex, FRANCE
    Pasquale Elena PhD Professor, Sanford Burnham Medical Research Institute University of California, San Diego
    Cattaruzza Fiore Research Scientist Pharmacologist at UCSF San Francisco, California

    PROGETTI
    2011. Progetto COST, per la Cooperazione Europea in Scienza e Tecnologia, che permette la coordinazione europea di attività di ricerca finanziate a livello nazionale. COST Action BM904 (Biomedicina e Bioscienze Molecolari) dal titolo : "HDL, dalla conoscenza biologica all'applicazione clinica".
    2011. Progetto di Ricerca Scientifica dal titolo “Caratterizzazione di AI-MI-AI-MI ricombinante (da semi di riso)” in collaborazione con il Prof. G. Franceschini e la Prof. L. Calabresi dell’Università degli Studi di Milano.
    2010. Progetto di Ricerca Scientifica dal titolo “Lupus eritematoso sistemico e aterosclerosi”, in collaborazione con il Prof. P.L. Meroni dell’Università degli Studi di Milano finanziato dal gruppo Italiano per la lotta contro il Lupus Eritematoso Sietemico (LES).
    2009-2011. Progetto di Ricerca SCietifica DiAL-ER/ADSL finanziato dalla regione Emilia Romagna dal titolo: “Diagnostica Avanzata in lipidologia- Advanced Diagnostic Support in Lipidology: role of genotypic, phenotypic and functional evaluation of lipoproteins in dislipidemias”.
    2009-2011 Progetto Scientifico finanziato da Cariplo: HDL QUANTITY OR QUALITY TO IMPROVE CARDIOVASCULAR PREVENTION: INSIGHTS FROM INHERITED HDL DISORDERS;
    2005. Progetto di Ricerca Scientifica Cofin 2005 “Fisiopatologia delle lipoproteine plasmatiche ad alta densità (HDL): un approccio integrato”.
    2005 Progetto Scientifico MURST. “REGOLAZIONE GENETICA E FARMACOLOGICA DEL TRASPORTO INVERSO DEL COLESTEROLO”
    2001. Progetto di Ricerca Scientifica FIRB “Nuove strategie per la prevenzione ed il controllo dell'ischemia cerebrale su base vascolare: ruolo dei meccanismi infiammatori e proteolitici”.
    2000. Consorzio Europeo V programma quadro 1999 Progetto QLG1-1999-01007 "Macrophage function and stability of the atherosclerotic plaque" (MAFAPS).
    2000. Progetto di Ricerca Scientifica Cofin 2000 “Deficit familiari delle lipoproteine ad alta densità. Aspetti genetici, biochimici e clinici”.
    2000. Progetto Scientifico MURST. "DEFICIT FAMILIARE DI LIPOPROTEINE AD ALTA DENSITA' (HDL): STUDI CELLULARI DEI DIFETTI DI EFFLUSSO DI COLESTEROLO E FOSFOLIPIDI"
    1998. Progetto Scientifico MURST. “Capacita' di stimolo dell'efflusso cellulare di colesterolo di sieri e frazioni lipoproteiche isolati da pazienti con ipoalfa- e iperalfa-lipoproteinemie primitive”
    1997. National Drugs Project in 1997-2000. Progetto Nazionale con Tecnofarmaci S.C.p.A. Roma, Italia
    Progetto Scientifico “Studio dei meccanismi responsabili delle alterazioni motorie del tratto digerente superiore nella malattia di Parkinson sperimentale” su finanziamento PRIN 2009
    Progetto Scientifico “Modulazione Farmacologica del sistema serotoninergico nell’ischemia intestinale” su finanziamento PRIN 2007
    Progetto Scientifico “Toxicological study related to 3-MCPD esters” su finanziamento EFSA

    PUBBLICAZIONI SELEZIONATE
    Franceschini G, Favari E, Calabresi L, Simonelli S, Bondioli A, Adorni MP, Zimetti F, Gomaraschi M, Coutant K, Rossomanno S, Niesor EJ, Bernini F, Benghozi R.
    Differential effects of fenofibrate and extended-release niacin on high-density lipoprotein particle size distribution and cholesterol efflux capacity in dyslipidemic patients.
    J Clin Lipidol. 2013 Sep-Oct;7(5):414-22.

    Zanotti I, Greco D, Lusardi G, Zimetti F, Potì F, Arnaboldi L, Corsini A, Bernini F.
    Cyclosporine a impairs the macrophage reverse cholesterol transport in mice by reducing sterol fecal excretion.
    PLoS One. 2013 Aug 9;8(8):e71572.

    Gomaraschi M, Ossoli A, Favari E, Adorni MP, Sinagra G, Cattin L, Veglia F, Bernini F, Franceschini G, Calabresi
    Inflammation impairs eNOS activation by HDL in patients with acute coronary syndrome.
    Cardiovasc Res. 2013 Oct 1;100(1):36-43.

    Adorni MP, Ronda N, Bernini F, Favari E.
    Rac1 and cholesterol metabolism in macrophage.
    J Cardiovasc Pharmacol. 2013 Nov;62(5):418-24.

    Minicocci I, Cantisani V, Poggiogalle E, Favari E, Zimetti F, Montali A, Labbadia G, Pigna G, Pannozzo F, Zannella A, Ceci F, Ciociola E, Santini S, Maranghi M, Vestri A, Ricci P, Bernini F, Arca M.
    Functional and morphological vascular changes in subjects with familial combined hypolipidemia: an exploratory analysis.
    Int J Cardiol. 2013 Oct 9;168(4):4375-8.

    Ronda N, Favari E, Borghi MO, Ingegnoli F, Gerosa M, Chighizola C, Zimetti F, Adorni MP, Bernini F, Meroni PL.
    Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus.
    Ann Rheum Dis. 2013 Apr 5. [Epub ahead of print]

    Caselli C, Lionetti V, Cabiati M, Prescimone T, Aquaro GD, Ottaviano V, Bernini F, Mattii L, Del Ry S, Giannessi D
    Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model.
    Cardiovasc Diabetol. 2012 Nov 19;11:143.

    Favari E, Ronda N, Adorni MP, Zimetti F, Salvi P, Manfredini M, Bernini F, Borghi C, Cicero AF.
    ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects.
    J Lipid Res. 2013 Jan;54(1):238-43.

    Fasano T, Zanoni P, Rabacchi C, Pisciotta L, Favari E, Adorni MP, Deegan PB, Park A, Hlaing T, Feher MD, Jones B, Uzak AS, Kardas F, Dardis A, Sechi A, Bembi B, Minuz P, Bertolini S, Bernini F, Calandra S.
    Novel mutations of ABCA1 transporter in patients with Tangier disease and familial HDL deficiency.
    Mol Genet Metab. 2012 Nov;107(3):534-41.

    Adorni MP, Zimetti F, Puntoni M, Bigazzi F, Sbrana F, Minichilli F, Bernini F, Ronda N, Favari E, Sampietro T. Cellular Adorni MP, Zimetti F, Puntoni M, Bigazzi F, Sbrana F, Minichilli F, Bernini F, Ronda N, Favari E, Sampietro T. Cellular cholesterol efflux and cholesterol loading capacity of serum: effects of LDL-apheresis. J Lipid Res. 2012. In press.

    I. Zanotti, E. Favari, F. Bernini (2012). Cellular cholesterol efflux pathways: Impact on Intracellular Lipid Trafficking and Methodological Considerations . CURRENT PHARMACEUTICAL BIOTECHNOLOGY, vol. 13, p. 292-302.

    Adorni M.P., Favari E., Ronda N., Granata A., Bellosta S., Arnaboldi L., Corsini A., Gatti R., Bernini F. (2011). Free cholesterol alters macrophage morphology and mobility by an ABCA1 dependent mechanism. ATHEROSCLEROSIS, vol. 215(1), p. 70-76.

    Zanotti I, Maugeais C, Pedrelli M, Gomaraschi M, Salgam P, Calabresi L, Bernini F, Kempen H. (2011) The thienotriazolodiazepine Ro 11-1464 increases plasma apoA-I and promotes reverse cholesterol transport in human apoA-I transgenic mice. Br J Pharmacol.;164(6):1642-51.

    Zanotti I, Pedrelli M, Potì F, Stomeo G, Gomaraschi M, Calabresi L, Bernini F. (2011)
    Macrophage, but not systemic, apolipoprotein E is necessary for macrophage reverse cholesterol transport in vivo. Arterioscler Thromb Vasc Biol.;31(1):74-80.

    Pisciotta L, Favari E, Magnolo L, Simonelli S, Adorni MP, Sallo R, Fancello T, Zavaroni I, Ardigò D, Bernini F, Calabresi L, Franceschini G, Tarugi P, Calandra S, Bertolini S. (2010) Characterization of three kindreds with familial combined hypolipidemia caused by loss-of-function mutations of ANGPTL3. Circ Cardiovasc Genet.;5(1):42-50.

    Ardigò D., Bernini F., Borghi C., Calandra S., Cicero A.F.G., Favari E., Fellin R., Franzini L., Vigna B.G., Zimetti F., Zavaroni I, ON BEHALF OF THE ADSL PROJECT INVESTIGATORS (2010). Advance diagnostic support in lipidology project: role for phenotipic and functional evaluation of lipoproteins in dyslipidemias. Clinical Lipidology, vol. 5(3); p. 329-337.

    Favari E, Calabresi L, Adorni MP, Jessup W, Simonelli S, Franceschini G, Bernini F. (2009)
    Small discoidal pre-beta1 HDL particles are efficient acceptors of cell cholesterol via ABCA1 and ABCG1.
    Biochemistry. 24;48(46):11067-74.

    Calabresi L, Nilsson P, Pinotti E, Gomaraschi M, Favari E, Adorni MP, Bernini F, Sirtori CR, Calandra S, Franceschini G, Tarugi P (2009). A novel homozygous mutation in CETP gene as a cause of CETP deficiency in a Caucasian kindred. Atherosclerosis.;205(2):506-11.

    Calabresi L, Favari E, Moleri E, Adorni MP, Pedrelli M, Costa S, Jessup W, Gelissen IC, Kovanen PT, Bernini F, Franceschini G. (2009). Functional LCAT is not required for macrophage cholesterol efflux to human serum. Atherosclerosis.;204(1):141-6. Epub 2008 Sep 6.

    Pisciotta L, Bocchi L, Candini C, Sallo R, Zanotti I, Fasano T, Chakrapani A, Bates T, Bonardi R, Cantafora A, Ball S, Watts G, Bernini F, Calandra S, Bertolini S. (2009) Severe HDL deficiency due to novel defects in the ABCA1 transporter. J Intern Med.;265(3):359-72.

    Zanotti I, Potì F, Pedrelli M, Favari E, Moleri E, Franceschini G, Calabresi L, Bernini F. (2008)
    The LXR agonist T0901317 promotes the reverse cholesterol transport from macrophages by increasing plasma efflux potential. J Lipid Res.;49(5):954-60. Epub 2008 Feb 5.

    Favari E, Gomaraschi M, Zanotti I, Bernini F, Lee-Rueckert M, Kovanen PT, Sirtori CR, Franceschini G, Calabresi L. (2007). A unique protease-sensitive high density lipoprotein particle containing the apolipoprotein A-I(Milano) dimer effectively promotes ATP-binding Cassette A1-mediated cell cholesterol efflux.
    J Biol Chem. 23;282(8):5125-32.

    Favari E, Zanotti I, Zimetti F, Ronda N, Bernini F, Rothblat GH. (2004)
    Probucol inhibits ABCA1-mediated cellular lipid efflux.
    Arterioscler Thromb Vasc Biol.;24(12):2345-50. Epub 2004 Oct 28.

    Favari E, Lee M, Calabresi L, Franceschini G, Zimetti F, Bernini F, Kovanen PT. (2004)
    Depletion of pre-beta-high density lipoprotein by human chymase impairs ATP-binding cassette transporter A1- but not scavenger receptor class B type I-mediated lipid efflux to high density lipoprotein.
    J Biol Chem. 12;279(11):9930-6.