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OXIDANTS AND ANTIOXIDANTS IN BIOLOGY BOOK OF ABSTRACTS: ADDENDUM 7-10 SEPTEMBER 2005 ALBA, ITALY Oxygen Club of California University of Turin

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Page 1: Oxygen Club University of California of Turinoxyclubcalifornia.org/OCC/pdf/addendum.pdf · Resveratrol protects against 4-Hydroxynonenal-induced apoptosis: a role for JNK, AP-1 and

OXIDANTS AND ANTIOXIDANTS IN BIOLOGY

BOOK OF ABSTRACTS: ADDENDUM

7-10 SEPTEMBER 2005ALBA, ITALY

Oxygen Clubof California

Universityof Turin

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OXIDANTS AND ANTIOXIDANTS IN BIOLOGY

A MEETING IN HONOR OFANGELO AZZI

7-10 SEPTEMBER 2005ALBA, ITALY

____________

A JOINT MEETING OFOXYGEN CLUB OF CALIFORNIA

UNIVERSITY OF TURIN

_____________

ORGANIZERS

Giuseppe PoliDEPARTMENT OF CLINICAL AND BIOLOGICAL SCIENCES, UNIVERSITY OF TURIN,

SAN LUIGI HOSPITAL, ORBASSANO, TURIN, ITALY

Helmut SiesINSTITUT FÜR BIOCHEMIE UND MOLEKULARBIOLOGIE I,

HEINRICH-HEINE-UNIVERSITÄT DÜSSELDORF, DÜSSELDORF, GERMANY

Enrique CadenasDEPARTMENT OF MOLECULAR PHARMACOLOGY & TOXICOLOGY, SCHOOL OF PHARMACY,

UNIVERSITY OF SOUTHERN CALIFORNIA, LOS ANGELES, CA, USA

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CONTENTS

ADDITIONAL POSTER ABSTRACTS ........235

LIST OF PARTICIPANTS................240

LIST OF SPONSORS....................264

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Resveratrol protects against 4-Hydroxynonenal-induced apoptosis: a role for JNK, AP-1 and caspases.

Ozgur Kutuk1, Giuseppe Poli2, Huveyda Basaga1

1Biological Sciences and Bioengineering Program, Sabanci Univ,34956 Tuzla, Istanbul,Turkey, e-mail: [email protected]

2Department of Clinical and Biological Sciences University of Turin atSt. Luigi Gonzaga Hospital,10043-Orbassano, Turin, Italy.

In the present study we have studied the effect of resveratrolin signal transduction mechanisms leading to apoptosis in3T3 fibroblasts when exposed to one of the major endproduct of oxidized fatty acid metabolism, 4-hydroxynonenal (HNE). Mitogen-activated protein kinases(MAP kinases) and various caspases have been proposed tomediate stress-induced apoptosis in many cell types. HNEinduced early activation of JNK and p38 proteins butdownregulated the basal activity of ERK 1/2. We were alsoable to demonstrate the release of cytochrome c frommitochondria, caspase-9 and caspase-3 activation as shownby active caspase fragments and fluorometric caspaseassays. Treatment of fibroblasts with specific inhibitors ofMAPKs and caspases provided further mechanisticevidence for JNK, caspase-9 and caspase-3 involvement butneither p38 nor ERK 1/2 in mediating HNE-inducedapoptosis. Studies undertaken by MAPK and caspaseinhibitors as well as resveratrol indicated that resveratrolwas as effective as JNK inhibitor in preventing JNK andcaspase activation hence apoptosis. Increase in c-Jun andphospho-c-Jun and decrease in c-Fos protein levels tookplace within 1 h of HNE treatment which was accompaniedby an increase in the DNA binding of AP-1. This effectcould be overcome by pretreatment of cells with resveratrolas shown by immunoblots and gel shift assays.Overexpression of dominant negative c-Jun and JNK1

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prevented HNE-induced apoptosis, which indicates a rolefor JNK-c-Jun/AP-1 pathway in HNE-induced apoptosis.In light of the JNK-dependent induction of c-Juntranscription and AP-1 upregulation induced by HNE andthe protective role of resveratrol, these data may show acritical potential role for JNK in the cellular responseagainst toxic products of lipid peroxidation. In this respectresveratrol acting through MAP kinase pathways andspecifically on JNK could have a role other than acting asan antioxidant.

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Oncolyn inhibits telomerase activity, induce apoptosis ofcancer cells, cause regression and clinical remission ofsolid tumors

Arthur H.K. DJang, M.D., Ph D.1Lai Zho-Sheng, M.S.2, Zhou Dian-Yuan, M.D. 2, M.Bud Nelson, Ph.D.,J.D.1, Mikhael Adams, N.D.3, Jiang Bai, M.D., Ph.D. 2, Zhang Zhenshu,

M.D., Ph.D. 2, Zhang Yali, M.D., Ph.D. 2, Zhang Yanshu, M.B.,4 ,DimitriosGalaris, Ph.D.5

Santé International, Inc., New York, USA, 1, Institute of Digestive Medicine, FirstMilitary Medical University, China, 2, Renascent Integral Health Centre, Toronto,Canada, 3, North China Mining Medical College, China,4 , University of IoanninaGreece, 5

In general, telomerase expression is a hallmark of cancer.Telomerase activity indicates the capacity for malignant cells’unlimited proliferation and immortality. Telomerase inhibitorsare attractive agents against this phenomenon.There are intenseworldwide efforts, 1, 2, for this endeavor; i.e, to discover agentsthat selectively destroy cancer cells without harming normaltissue. Oncolyn® has been demonstrated previously to possessanti-oxidative, anti-inflammatory, anti-angiogensis, anti-metastasis, immune augmentation, dismutagenic andcytoprotective activities, as well as, promote cancer cellapoptosis.Oncolyn was demonstrated to protect DNA against H2O2, silicaand asbestos particles by single cell gel electrophoresis andhistopathology. Effective management of malignantmesothelioma verified by CT will be included.The present data further demonstrates the positive correlation oftelomerase inhibition by Oncolyn with cancer cell apoptosis, inproviding a molecular basis for Oncolyn’s anti-cancer function,prevention and therapy.Oncolyn is composed of edible plant extracts with mainingredients including flavonoids, polyphenols, phenolic acidsand saponins. It protects skin from UV damage, respiratory

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system from silica and asbestos, endothelium from ox LDL. Ithas shown anti-cancer function in nude mouse against variouscancer cells implants both for prevention and therapy.Inhibition of telomerase results in erosion of telomeres, andeventful cessation of cell proliferation and apoptosis.Tables of telomerase inhibition with correlation of cancer cells’apoptosis and summary of clinical application of Oncolynagainst various malignancies will be included.

Literature cited1 Enzyme stopper combats cancer, Science News, May 28, 2005, 167-3492 Efficacy of telomerase inhibitor drug discussion, American Association for Cancer Research2005, Annual Meeting, May, Anaheim, California.

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Ascorbate and nitrite react under physiologicallyrelevant conditions to give a novel product and not NO

Milos Filipovic1, Dragana Stanic1 and Vesna Niketic2

1 ICTM-Center for Chemistry, University of Belgrade2 Department of Chemistry, University of Belgrade

Nitric oxide, an important regulator of a variety ofbiological functions, is synthesized by complex enzymesknown as nitric oxide synthases. Recently, a novel pathwayfor NO production in humans that involves either directdisproportion or reduction of nitrite to NO under the acidicand/or highly reductional conditions was discovered. Thelatter includes ascorbic acid, which reduces nitrous acidrapidly into NO under acidic conditions. In the present workwe provide direct evidence that ascorbate and nitrite react atphysiological pH in 2:1 stoichiometry to yield a previouslyunidentified product: 3, 3’-[(hydroxyimino)bis(oxy)]bis-(ascorbic acid). The product was purified and its structurewas confirmed by 13C, 1H-NMR, IR spectra and MS-ESI.Product spontaneously decomposes releasing NO, whichwas detected electrochemically, and its bioactivityconfirmed with organ chamber method. Kinetics of NOrelease was determined by oxyhemoglobin assay. Transitionmetal ions (iron, copper) catalyze the release of nitric oxide.These findings are highly relevant for explaining thephenomena related to the nonenzymatic production of NOin human macro-phages and the nitrite-rich DietaryApproaches to Stop Hypertension-diet induced hypotensiveeffects. Furthermore, the product of ascorbate and nitritemay serve as a potential pharmacological donor of NO,which could decrease the vascular tone and increase thetissue blood flow.

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LIST OF PARTICIPANTS

Abbott Mariana Pedrinha [email protected]

Ahl Ing-Marie [email protected]

Albano Emanuele [email protected]

Aldini Giancarlo [email protected]

Ames Bruce [email protected]

Antunes Fernando Jose Nunes [email protected]

Aoki Yutaka France [email protected]

Aquilano Katia [email protected]

Aragno Manuela [email protected]

Arduini Alessandro [email protected]

Arkan Melek Canan [email protected]

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Arnér Elias [email protected]

Ashur Idan [email protected]

Augustin Wolfgang [email protected]

Azzi Angelo [email protected]

Baldovino Norman Italynorm82@libero-it

Banning Antje [email protected]

Basaga Huveyda [email protected]

Battino Maurizio [email protected]

Beretta Giangiacomo [email protected]

Bermejo Bescós Palma [email protected]

Bertoli Enrico [email protected]

Biasi Fiorella [email protected]

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Boccini Francesca [email protected]

Boguszewska Anna [email protected]

Borges Fernanda Portugal [email protected]

Boveris Alberto [email protected]

Brigelius-Flohé Regina [email protected]

Brito Paula [email protected]

Cadenas Enrique [email protected]

Calabrese Vittorio [email protected]

Calheiros Cruz Rita [email protected]

Canal Tiziana [email protected]

Canali Raffaella Italy [email protected]

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Carini Marina Italy [email protected]

Castello Laura [email protected]

Cavalca Viviana Italy [email protected]

Cavalieri Barbara [email protected]

Ceriello Antonio Italy [email protected]

Chamulitrat Walee [email protected]

Chessex Philippe Canada [email protected]

Chiarpotto Elena Italy [email protected]

Christen Stephan [email protected]

Cillard Josiane France [email protected]

Cillard Pierre France [email protected]

Cimino Francesco [email protected]

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Ciriolo Maria R. [email protected]

Comporti Mario Italy [email protected]

Cook Sarah L. UK [email protected]

Corona Giulia Italy [email protected]

Corti Alessandro [email protected]

Corvi Mora Paolo [email protected]

Coutinho Olga Pereira [email protected]

Cross Carrol E. USA [email protected]

Cutrin Juan Carlos Italy [email protected]

da Costa Ferreira Ana Maria [email protected]

Dalle Donne Isabella Italy [email protected]

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Davison Gareth [email protected]

Day Regina USA [email protected]

Degan Paolo Italy [email protected]

Del Val Greg [email protected]@excite.com

De Martino Angelo [email protected]

Dessì Maria Assunta [email protected]

Dever Gary UK [email protected]

Dianzani Mario Umberto [email protected]

Dickinson Dale A. [email protected],[email protected]

Djang Arthur H.K. [email protected]

Di Leva Agnese [email protected]

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Domenech de Antonio Elena [email protected]

Domenicotti Cinzia [email protected]

Dunker Manfred S. [email protected]

Eichhorn Judith [email protected]

Erridge Clett UK [email protected]

Escobar Javier J. [email protected]

Esposito Franca [email protected]

Favier Alain [email protected]

Fehlmann Max [email protected]

Feijoo Montserrat Spain [email protected]

Felici Emanuela [email protected]

Filipovic Milos R. Serbia and [email protected]

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Filomeni Giuseppe [email protected]

Finckh Barbara [email protected]

Flohé Leopold [email protected]

Frade Joao [email protected]

Fraga César [email protected]

Franzini Maria Italy [email protected]

Froio Teresa [email protected]

Galaris Dimitrios [email protected]

Galletti Sara Italy [email protected]

Gamba Paola [email protected]

Gambini Juan [email protected]

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Gargiulo Simona [email protected]

Gellerman Werner [email protected]

Giusti Anna Maria [email protected]

Gómez Gómez Carmen [email protected]

González Rául [email protected]

Gruber Florian [email protected]

Guarnieri Serena Italy [email protected]

Gwozdzinski Krzysztof [email protected]

Han Derick [email protected]

Handa Osamu [email protected]@koto.kpu-m.ac.jp

Hari Siva P. [email protected]

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Hatao Masato [email protected]

Heller Regina [email protected]

Hernandez Eva UK [email protected]

Hiller Karl-O. [email protected]

Hofstetter Dustin [email protected]

Holmgren Arne [email protected]

Ichijo Hidenori [email protected]

Iles Karen E. USA [email protected]

Izzotti Alberto [email protected]

Jansson Patric J. [email protected]

Jessup Wendi [email protected]

Jones Dean [email protected]

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Junqueira Virginia [email protected]

Kadl Alexandra [email protected]

Kartal-Özer Nesrin [email protected]

Kambe Tetsuya [email protected]

Kawanishi Shouske [email protected]@mb.med.kyoto-u.ac.jp

Klotz Lars Oliver [email protected]

Kokura Satoshi [email protected]

Kondo Norihiko [email protected]

Krutmann Jean [email protected]

Laggner Hilde Gard Austria [email protected]

Laranjinha Joao [email protected]

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Ledo Ana Margarida [email protected]

Leighton Federico Chile [email protected]

Leitinger Norbert [email protected]

Leonarduzzi Gabriella [email protected]

Leoncini Emanuela Italy [email protected]

Lillig Christopher Horst [email protected]

Lisovskaya Irina L. [email protected]

Livrea Maria A. [email protected]

Lloret Ana [email protected]

Lupino Stefania [email protected]

Maffei Facino Roberto [email protected]

Maggiora Marina [email protected]

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Maguire John USA [email protected]@yahoo.com

Maina Marco [email protected]

Maiorino Matilde [email protected]

Makarov Valery G. [email protected]

Makarova Marina N. [email protected]

Mann Giovanni [email protected]

Mantello Pierre [email protected]

Maraldi Tullia Italy [email protected]

Marcocci Lucia [email protected]

Marinari Umberto M. [email protected]

Markovic Jelena [email protected]

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Martina Valentino [email protected]

Martins Maria João [email protected]

Marzani Barbara Italy [email protected]

Mascia Cinzia [email protected]

Massarenti Paola [email protected]

Mastrocola Raffaella Italy [email protected]

Masutani Hiroshi [email protected]

Matsui Hirofumi Japan [email protected]

Meydani Mohsen [email protected]

Meydani Simin [email protected]

Milzani Aldo Italy [email protected]

Miranda-Vizuete Antonio [email protected]

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Mirault Marc-Edouard [email protected]

Mitjavila Maria Tersa [email protected]

Mora Nancy J [email protected]

Moulas Anargyros N [email protected]

Muntané Jordi [email protected]

Muzio Giuliana [email protected]

Nakamura Masao [email protected]

Natella Fausta [email protected]

Navarro Ana Spain [email protected]

Negre-Salvayre Anne [email protected]

Nesaretnam Kala [email protected]

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Neufang Gitta [email protected]

Nordstrom Tommy [email protected]

Nunes Carla Portugal [email protected]

Ogru Esra [email protected]

Oteiza Patricia USA [email protected]

Paker Lester USA [email protected]

Park Ah-Mee [email protected]

Pasternak Kazimierz Poland

Patel Mulchand USA [email protected]

Pena Deudero Juan Josè Spain [email protected]

Perrelli Maria Giulia [email protected]

Picklo Matthew J. [email protected]

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Pina Enrique Mexico [email protected]

Poli Giuseppe Italy [email protected]

Polidori Cristina Germany [email protected]

Pompella Alfonso [email protected]

Popova Natalia A. Russia [email protected]

Portes Pascal [email protected]

Pozzi Roberto [email protected]

Prata Cecilia Italy [email protected]

Pritsos Chris A. [email protected]

Pritsos Karen L. [email protected]

Pronzato Maria Adelaide [email protected]

Radi Rafael [email protected]

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Rallis Michail [email protected]

Ramadori Pierluigi [email protected]

Reimann Juergen [email protected]

Reiter Elker [email protected]

Rimbach Gerald [email protected]

Riso Patrizia [email protected]

Robbesyn Fanny [email protected]

Rogovin Jarrow L. [email protected]

Romano Antonino [email protected]

Romero Gomez Francisco J. [email protected]

Rossi Luisa [email protected]

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Royo Dolores [email protected]

Sakhi Amrit Kaur [email protected]

Scalbert Augustin [email protected]

Schaur Rudolf J. [email protected]

Schwarzer Evelin [email protected]

Sena Cristina [email protected]

Serviddio Gaetano [email protected]

Shamsaei Elham [email protected]

Shcherbachenko Irina M [email protected]

Sies Helmut [email protected]

Silva Joao Pedro Portugal [email protected]

Simon-Giavarotti Karin [email protected]

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Sitia Roberto [email protected]

Smith Mark [email protected]

Soodaeva Svetlana K. [email protected]

Sottero Barbara [email protected]

Sowden Rebecca [email protected]

Spickett Corinne [email protected]

Squillerio Isabella [email protected]

Stahl Wilhelm [email protected]

Stanic Dragana Serbia and [email protected]

Steiling Heike [email protected]

Sukiasyan Astghik [email protected]

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Sury Matthias [email protected]

Suzuki Hisanori [email protected]

Suzuki Yuichiro [email protected]

Sztanke Malgorzata Poland

Takagi Tomohisa [email protected]

Tamborra Rosanna [email protected]

Tarozzi Andrea Italy [email protected]

Tedesco Doriana [email protected]

Terao Junji [email protected]

Tessitore Luciana [email protected]

Tikhonov Vladimir P. [email protected]

Trappoliere Marco [email protected]

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Traverso Nicola [email protected]

Tsuji Tomoko [email protected]

Uchida Koji [email protected]

Unterhorst Goetz Italy [email protected]

Ursini Fulvio [email protected]

Valacchi Giuseppe [email protected]

Valdez Laura Beatriz [email protected]

Valles Soraya L. [email protected]

Veglia Fabrizio [email protected]

Vernole Patrizia Italy [email protected]

Vidali Matteo Italy [email protected]

Vigliocco Giorgia [email protected]

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Vina José [email protected]

Vinokur Vladimir [email protected]

Violi Francesco [email protected]

Vita Joseph [email protected]

Vizio Barbara [email protected]

Voß Peter [email protected]

Williamson Gary [email protected]

Wiswedel Ingrid [email protected]

Wright James S. [email protected]@pigeon.carleton.ca

Yodoi Junji [email protected]

Zambonin Laura [email protected]@biocfarm.unibo.it

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Zaobornyj Tamara [email protected]@ffyb.uba.ar

Zarkovic Neven [email protected]

Zarkovic Kamelia [email protected]

Zentella Martha [email protected]

Zingaro Lorenzo [email protected]

Zingg Jaun Mike [email protected]

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SPONSORS

Fondazione FerreroCavalieri Ottolenghi Foundation

BASF

Abkit, Inc.Actimex

Alexis BiochemicalsBeiersdorf AG

Cassella-med GmbHCognis, GermanyDanone Vitapole

Dompè PharmaceuticalDSEA, Dietary supplement Education Alliance

DSM Nutritional Products, Inc.Fratelli Ceretto

Jarrow FormulasJarrow Industries

Johnson & JohnsonLeiner Health Products

LI ConsultingNestlé

NovartisOrthomol GmbH

Osato Research InstitutePharmanex Research Institute

PhosphagenicsSchool of Pharmacy, University of Southern California

The Colgate Palmolive CompanyTown of Alba

Turin Committee for 2006 Winter Olympics