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      Possible Involvement of Oxidative Stress in Salivary Gland of Patients with Sjögren’s Syndrome

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          Abstract

          Objective: To determine the involvement of oxidative stress in the salivary gland of patients with Sjögren’s syndrome (SS). Methods: Oxidative damage to the gland was measured by 8-hydroxy-2′-deoxyguanosine (8-OHdG) and hexanoyl-lysine (HEL) using the SS saliva. In addition, lactate dehydrogenase (LDH) and mitochondrial glutamic-oxaloacetic transaminase (m-GOT), both general markers for cell damage, were also analyzed. Results: Increased levels of 8-OHdG and HEL were found in the saliva of SS patients, but not in that of patients with other salivary gland dysfunction or of healthy individuals. Levels of LDH and m-GOT were significantly correlated with 8-OHdG and HEL levels, respectively. Furthermore, the increased levels of 8-OHdG and HEL were also correlated in the SS saliva. Conclusion: These findings suggested the involvement of oxidative stress in glandular tissue destruction in SS. It was indicated that the detection of 8-OHdG and HEL in the saliva may become a useful tool for the diagnosis of SS.

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          Oxidative stress as a mediator of apoptosis.

          Many agents which induce apoptosis are either oxidants or stimulators of cellular oxidative metabolism. Conversely, many inhibitors of apoptosis have antioxidant activities or enhance cellular antioxidant defenses. Mammalian cells exist in a state of oxidative siege in which survival requires an appropriate balance of oxidants and antioxidants. Thomas Buttke and Paul Sandstrom suggest that eukaryotic cells may benefit from this perilous existence by invoking oxidative stress as a common mediator of apoptosis.
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            DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems.

            When cells are exposed to oxidative stress, DNA damage frequently occurs. The molecular mechanisms causing this damage may include activation of nucleases and direct reaction of hydroxyl radicals with the DNA. Several oxygen-derived species can attack DNA, producing distinctive patterns of chemical modification. Observation of these patterns and measurement of some of the products formed has been used to determine the role of different oxygen-derived species in DNA cleavage reactions, to assess the extent of oxidative damage to DNA in vivo and to investigate the mechanism of DNA damage by ionizing radiation and chemical carcinogens.
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              Redox regulation of cellular activation.

              Growing evidence has indicated that cellular reduction/oxidation (redox) status regulates various aspects of cellular function. Oxidative stress can elicit positive responses such as cellular proliferation or activation, as well as negative responses such as growth inhibition or cell death. Cellular redox status is maintained by intracellular redox-regulating molecules, including thioredoxin (TRX). TRX is a small multifunctional protein that has a redox-active disulfide/dithiol within the conserved active site sequence: Cys-Gly-Pro-Cys. Adult T cell leukemia-derived factor (ADF), which we originally defined as an IL-2 receptor alpha-chain/Tac inducer produced by human T cell lymphotrophic virus-I (HTLV-I)-transformed T cells, has been identified as human TRX. TRX/ADF is a stress-inducible protein secreted from cells. TRX/ADF has both intracellular and extracellular functions as one of the key regulators of signaling in the cellular responses against various stresses. Extracellularly, TRX/ADF shows a cytoprotective activity against oxidative stress-induced apoptosis and a growth-promoting effect as an autocrine growth factor. Intracellularly, TRX/ADF is involved in the regulation of protein-protein or protein-nucleic acid interactions through the reduction/oxidation of protein cysteine residues. For example, TRX/ADF translocates from the cytosol into the nucleus by a variety of cellular stresses, to regulate the expression of various genes through the redox factor-1 (Ref-1)/APEX. Further studies to clarify the regulatory roles of TRX/ADF and its target molecules may elucidate the intracellular signaling pathways in the responses against various stresses. The concept of "redox regulation" is emerging as an understanding of the novel mechanisms in the pathogenesis of several disorders, including viral infections, immunodeficiency, malignant transformation, and degenerative disease.
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                Author and article information

                Journal
                PAT
                Pathobiology
                10.1159/issn.1015-2008
                Pathobiology
                S. Karger AG
                1015-2008
                1423-0291
                2006
                February 2007
                23 February 2007
                : 73
                : 5
                : 252-260
                Affiliations
                Departments of aPathology and bGeriatric Dentistry, and cSecond Department of Oral and Maxillofacial Surgery, Tsurumi University School of Dental Medicine, Yokohama, Japan
                Article
                98211 Pathobiology 2006;73:252–260
                10.1159/000098211
                17314496
                9047db2f-3938-46f2-aeed-c8bd82bf472b
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 12 September 2006
                : 17 October 2006
                Page count
                Figures: 7, Tables: 2, References: 56, Pages: 9
                Categories
                Original Paper

                Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Saliva,Salivary gland,Autoimmunity,Oxidative stress

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