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      Beneficial Effects of Wheat Gluten Hydrolysate to Extend Lifespan and Induce Stress Resistance in Nematode Caenorhabditis elegans

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          Abstract

          Previous studies have showed that wheat gluten hydrolysate (WGH) has the anti-oxidative property. In the present study, we examined the possible safety property of WGH and the beneficial effects of WGH to extend lifespan and induce stress resistance using nematode Caenorhabditis elegans as the in vivo assay system. We found that WGH at concentrations of 0.1–1 mg/mL did not cause lethality, influence development, alter locomotion behavior and brood size, and induce significant intestinal autofluorescence and reactive oxygen species (ROS) production in young adults. Treatment with 0.1–1 mg/mL of WGH significantly extended lifespans of nematodes under the normal conditions. Moreover, WGH treatment significantly inhibited the induction of intestinal autofluorescence and suppressed the decrease in locomotion behavior during the aging process of nematodes. Furthermore, pre-treatment with 1 mg/mL of WGH significantly suppressed the adverse effects caused by heat-stress or oxidative stress on nematodes as indicated by the alterations of both lifespan and intestinal ROS production. Therefore, WGH treatment is relatively safe and has beneficial effects on nematodes under both the normal conditions and the stress conditions.

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          Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology

          The nematode Caenorhabditis elegans has emerged as an important animal model in various fields including neurobiology, developmental biology, and genetics. Characteristics of this animal model that have contributed to its success include its genetic manipulability, invariant and fully described developmental program, well-characterized genome, ease of maintenance, short and prolific life cycle, and small body size. These same features have led to an increasing use of C. elegans in toxicology, both for mechanistic studies and high-throughput screening approaches. We describe some of the research that has been carried out in the areas of neurotoxicology, genetic toxicology, and environmental toxicology, as well as high-throughput experiments with C. elegans including genome-wide screening for molecular targets of toxicity and rapid toxicity assessment for new chemicals. We argue for an increased role for C. elegans in complementing other model systems in toxicological research.
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            Molecular basis of celiac disease.

            Celiac disease (CD) is an intestinal disorder with multifactorial etiology. HLA and non-HLA genes together with gluten and possibly additional environmental factors are involved in disease development. Evidence suggests that CD4(+) T cells are central in controlling an immune response to gluten that causes the immunopathology, but the actual mechanisms responsible for the tissue damage are as yet only partly characterized. CD provides a good model for HLA-associated diseases, and insight into the mechanism of this disease may well shed light on oral tolerance in humans. The primary HLA association in the majority of CD patients is with DQ2 and in the minority of patients with DQ8. Gluten-reactive T cells can be isolated from small intestinal biopsies of celiac patients but not of non-celiac controls. DQ2 or DQ8, but not other HLA molecules carried by patients, are the predominant restriction elements for these T cells. Lesion-derived T cells predominantly recognize deamidated gluten peptides. A number of distinct T cell epitopes within gluten exist. DQ2 and DQ8 bind the epitopes so that the glutamic acid residues created by deamidation are accommodated in pockets that have a preference for negatively charged side chains. Evidence indicates that deamidation in vivo is mediated by the enzyme tissue transglutaminase (tTG). Notably, tTG can also cross-link glutamine residues of peptides to lysine residues in other proteins including tTG itself. This may result in the formation of complexes of gluten-tTG. These complexes may permit gluten-reactive T cells to provide help to tTG-specific B cells by a mechanism of intramolecular help, thereby explaining the occurrence of gluten-dependent tTG autoantibodies that is a characteristic feature of active CD.
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              Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1.

              In Caenorhabditis elegans pretreatment with juglone, a generator of reactive oxygen species (ROS) provides a subsequently increased ROS-resistance. We investigated whether juglone at low or high concentrations when provided via the oral route in a liquid axenic medium affects normal lifespan of C. elegans. High juglone concentrations led to premature death, low concentrations were tolerated well and caused a prolongation of lifespan. Lifespan extension under moderate oxidative stress was associated with increased expression of small heat-shock protein HSP-16.2, enhanced glutathione levels, and nuclear translocation of DAF-16. Silencing or deletion of DAF-16 prevented the juglone-induced adaptations. RNA-interference for SIR-2.1 had the same effects as the deletion of DAF-16 but did not affect nuclear accumulation of DAF-16. Our studies demonstrate that DAF-16- and SIR-2.1-dependent alterations in gene expression after a ROS challenge lead to a lifespan extension in C. elegans as long as the stressor concentration does not exceed the saturable protective capacity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                9 September 2013
                : 8
                : 9
                : e74553
                Affiliations
                [1 ]College of Life Sciences, Nanjing Normal University, Nanjing, China
                [2 ]Nanjing Institute for Comprehensive Utilization of Wild Plants, Nanjing, China
                [3 ]School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China
                [4 ]Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, China
                University of Houston, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZZ DW. Performed the experiments: WZ TL ML LY HL. Analyzed the data: DS QW. Contributed reagents/materials/analysis tools: LS. Wrote the paper: ZZ DW.

                Article
                PONE-D-13-26403
                10.1371/journal.pone.0074553
                3767650
                24040279
                f30cf60e-671f-48e8-9d82-3c0ed588c061
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 June 2013
                : 3 August 2013
                Page count
                Pages: 6
                Funding
                This work was supported by Scientific Starting Fund from Changzhou University (ZMF11020011), National High Technology Research and Development Program of China (863 Program, 2011AA100802), National Agricultural Achievements Transformation Fund Project (03EFN217200345), National Science and Technology Support Program (2011BAD33B03), Specialized Research Fund for the Doctoral Program of Higher Education of China (20120092120064), and National Natural Science Foundation of China (No. 81172698, 81202233). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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