OCC 2010 B OF C LU A OXYGEN CLUB C L I N F E O OF CALIFORNIA R G N Y O2 I X A s O t ac tr E 4 ST 9 2010 A 19 BLISHED Abs ook of ook OXIDANTS AND ANTIOXIDANTS IN BIOLOGY B - ess TRANSLATIONAL REDOX SCIENCE r g n o CO-SPONSORED BY THE d C d LINUS PAULING INSTITUTE l r o W OOK OF BSTRACTS 010 010 B A 2 ’ CC O 17-20 MARCH, 2010 FESS PARKER’S DOUBLE TREE RESORT SANTA BARBARA, CALIFORNIA OXIDANTS AND ANTIOXIDANTS IN BIOLOGY TRANSLATIONAL REDOX SCIENCE 17-20 MARCH 2010 SANTA BARBARA, CALIFORNIA CONFERENCE SCIENTIFIC PROGRAM ORGANIZERS ORGANIZERS ___________________________ ____________________________ Chandan K. Sen Bruce N. Ames Dipak K. Das Enrique Cadenas César G. Fraga Dipak K. Das Thomas K. Hunt César G. Fraga Klaus Kraemer John Maguire Periannan Kuppusamy Lester Packer Lester Packer Junji Yodoi Chandan K. Sen Helmut Sies Roland Stocker Hideo Utsumi José Viña Junji Yodo 2 CONTENTS KEYNOTE ADDRESSES ...............................................................................................5 SESSION I WOUND HEALING................................................................................9 SESSION II REDOX SIGNALING AND INFLAMMATION.........................................19 SESSION III C ARDIOVASCULAR ............................................................................29 SESSION IV TRANSLATIONAL SCIENCE BY MICRONUTRIENTS............................35 SESSION V REDOX IMAGING................................................................................51 SESSION VI AGING ................................................................................................55 POSTERS ...................................................................................................................61 AUTHOR INDEX ......................................................................................................178 KEYNOTE ADDRESSES Novel infectious agents in human carcinogenesis: State and perspectives New horizons in HIV/AIDS Harald zur Hausen Luc Montagnier Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany World Foundation AIDS Research and Prevention, UNESCO, Paris, France During the past 30 years up to 21% of the global cancer inci- Combined antiretroviral therapy (ARV) keeps the virus multipli- dence has been linked to infectious events, involving specific viral, cation to a low level as evidenced by the disappearance of viral RNA bacterial and parasitic agents. Particularly the discovery of a role in the blood of HIV infected patients but does not completely elimi- of Hepatitis B virus in hepatocellular carcinomas and of high risk nate the virus: there is a viral reservoir which remains untouched even human papillomaviruses (HPV) in cervical, other anogenital and after long term treatment and regenerates viral multiplication if the oropharyngeal cancers triggered novel approaches in cancer pre- treatment is interrupted. vention by vaccination. A global application of these vaccines We have approached the identification of this reservoir by a new theoretically could reduce the cancer risk in females by 12-14%, in technology based on the detection of electromagnetic signals pro- males by 4-5%. Mechanisms of cell transformation by infectious duced by some viral and bacterial DNAs, in particular by HIV DNA agents will be analyzed. Even in cases where infectious agents act sequences. Thus, we have detected a reservoir of HIV DNA in the as direct carcinogens and where their persistence is necessary for blood of all patients treated by ARV, both in the plasma and in the the maintenance of the carcinogenic phenotype, additional modifi- erythrocyte fraction. cations of the host cell genome emerge as necessary events for ma- This will constitute a useful biomarker for complementary thera- peutics aimed at eradicating the virus infection such as immunother- lignant proliferation. Considerations will be presented to analyze apy and antioxidants. even cancers not yet linked to infectious events for a possible in- volvement of exogenous agents in their etiology. This involves in part cancers increased under immunosuppression, but also those with a reduced or not elevated incidence after immunosuppression. Malignant tumors arising either in the sequence of other infections will also be discussed or where those infections appear to exert protective functions. Finally potential synergistic effects of nutri- tional carcinogens with virus infections deserve further attention. 6 7 SESSION I WOUND HEALING Hyperbaric oxygen therapy and stem cell response in Homing to hypoxia: The role of oxygen tension in progenitor wound healing cell trafficking to sites of injury Omaida C. Velazquez The DeWitt Daughtry Family Department of Surgery, Leonard M. J. Glotzbach, H. Thangarajah, N. Vial, and G.C. Gurtner Miller School of Medicine, University of Miami, Miami, FL, USA Department of Surgery, Stanford University, Stanford, CA, 94305 Wound healing occurs because of events in two compartments. Within the bone marrow, various signaling pathways trigger mobiliza- The isolation of circulating endothelial progenitor cells (EPCs) tion of bone marrow-derived progenitor cells (EPC) and other has altered our understanding of how new blood vessels form in stem/progenitor cells involved in the healing cascade. Within the wound, neovascularization occurs because of local chemical factors adult tissues (heart, brain, wounds) following injury. While an ex- that stimulate adjacent cells (angiogenesis) and because of recruited act characterization of the responsible cell(s) remains elusive, it is circulating EPC that differentiate into vascular channels (vasculogene- clear that a subset of the bone marrow is capable of selectively sis). Many chemo/cytokines trigger EPC release via induction of met- trafficking to areas of tissue damage and forming blood vessels de alloproteinase-9 (MMP-9) in bone marrow, and Nitric Oxide (.NO) has novo through a cascade of adhesion, migration, proliferation and been linked to this process. We have found that HBO2 will stimulate tubulization. We have identified the chemokine axis CXCR4/ EPC recruitment and augment healing of diabetic wounds in mice. Our . stromal cell-derived factor-1 (SDF-1) as a critical mediator of studies demonstrated that HBO2 increases synthesis of NO in bone ischemia-specific progenitor trafficking and have demonstrated marrow, increases the concentration of circulating stem cell factor, and that SDF-1 is transcriptionally regulated by tissue oxygen tension stimulates EPC mobilization. If NOS was inhibited, all of the HBO2- via hypoxia-inducible factor-1 (HIF-1). Since both hypoxia and mediated events were blocked. Therefore, HBO2 appears to stimulate EPC mobilization by a .NO dependent mechanism. We believe the se- SDF-1 are also observed in the bone marrow niche, hypoxia may . be a fundamental stimulus for progenitor cell trafficking and func- quence of events is as follows: HBO2 NOS NO nitrosylation tion. After homing to injured tissue, both bone marrow-derived of MMP9cleavage of membrane-bound SCFSCF prompts EPC proliferation and mobilization EPC released into peripheral circula- and adipose-derived mesenchymal stem cells respond to hypoxia tion. However, EPC homing to areas in need of neovascularization by adopting a proangiogenic phenotype by proliferating, forming (such as a wound) does not appear to be specifically impacted by tubes and secreting vascular growth factors. Alterations in hypoxia HBO2. Homing signals such as Stromal Derived Growth Factor 1 alpha signaling may contribute to the pathophysiology of diseases with (SDF-1) appear to be more important for EPC homing. We have de- known defects in blood vessel growth, such as diabetes. It appears termined that (1) Diabetes results in decreased eNOS phosphorolation that hyperglycemia directly alters the molecular structure and func- within the bone marrow, thus reducing mobilization of endothelial tion of HIF-1 and its cofactors by methylglyoxylation of specific progenitor cells (EPCs), (2) Diabetes results in downregulation of arginine residues preventing assembly of transcriptional machin- SDF-1 within wounds, thus decreasing EPC homing to wounds, and ery. This results in both decreased angiogenesis and decreased re- (3) these two key diabetes-associated impairments in wound healing cruitment of progenitor cells to areas of ischemia in diabetes. This and neovascularization may be reversed by the combination of sys- suggests that the end manifestations of diabetes may be the result temic hyperoxia (to increase EPC mobilization) and wound SDF-1 of impaired hypoxia signaling following injury. injections (to increase EPC homing). Most recently, we have further determined that SDF-1 may mediate its EPC-homing effects via ef- Supported by NIH grants RO1-EB002265 and RO1-AG025016 fects on specific adhesion molecules. 10 11 Impaired resolution of wound in diabetes Mathematical modeling of the role of oxygen in Sashwati Roy non-ischemic and ischemic wound healing Comprehensive Wound Center, Department of Surgery, The Ohio State University Medical Center, Columbus, OH Avner Friedman Acute inflammation resolves by mechanisms that are not fully understood. Persistence of the inflammatory response (chronic in- Mathematical Bioscience Institute, Ohio State University, flammation) can lead to scarring and loss of organ function. An ac- Columbus, OH, USA tively coordinated program of resolution initiates in the first few hours after an inflammatory response is triggered by tissue injury. It is well known that