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      Influence of Acute Exercise on DNA Repair and PARP Activity before and after Irradiation in Lymphocytes from Trained and Untrained Individuals

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          Abstract

          Several studies indicate that acute exercise induces DNA damage, whereas regular exercise increases DNA repair kinetics. Although the molecular mechanisms are not completely understood, the induction of endogenous reactive oxygen species (ROS) during acute exhaustive exercise due to metabolic processes might be responsible for the observed DNA damage, while an adaptive increase in antioxidant capacity due to regular physical activity seems to play an important protective role. However, the protective effect of physical activity on exogenously induced DNA damage in human immune cells has been poorly investigated. We asked the question whether individuals with a high aerobic capacity would have an enhanced response to radiation-induced DNA damage. Immune cells are highly sensitive to radiation and exercise affects lymphocyte dynamics and immune function. Therefore, we measured endogenous and radiation-induced DNA strand breaks and poly (ADP-ribose) polymerase-1 (PARP1) activity in peripheral blood mononuclear cells (PBMCs) from endurance-trained (maximum rate of oxygen consumption measured during incremental exercise V’O 2max > 55 mL/min/kg) and untrained (V’O 2max < 45 mL/min/kg) young healthy male volunteers before and after exhaustive exercise. Our results indicate that: (i) acute exercise induces DNA strand breaks in lymphocytes only in untrained individuals, (ii) following acute exercise, trained individuals repaired radiation-induced DNA strand breaks faster than untrained individuals, and (iii) trained subjects retained a higher level of radiation-induced PARP1 activity after acute exercise. The results of the present study indicate that increased aerobic fitness can protect immune cells against radiation-induced DNA strand breaks.

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          Most cited references74

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          Poly(ADP-ribose): novel functions for an old molecule.

          The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.
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            Single-strand break repair and genetic disease.

            Hereditary defects in the repair of DNA damage are implicated in a variety of diseases, many of which are typified by neurological dysfunction and/or increased genetic instability and cancer. Of the different types of DNA damage that arise in cells, single-strand breaks (SSBs) are the most common, arising at a frequency of tens of thousands per cell per day from direct attack by intracellular metabolites and from spontaneous DNA decay. Here, the molecular mechanisms and organization of the DNA-repair pathways that remove SSBs are reviewed and the connection between defects in these pathways and hereditary neurodegenerative disease are discussed.
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              Is physical activity or physical fitness more important in defining health benefits?

              We addressed three questions: 1) Is there a dose-response relation between physical activity and health? 2) Is there a dose-response relation between cardiorespiratory fitness and health? 3) If both activity and fitness have a dose-response relation to health, is it possible to determine which exposure is more important? We identified articles by PubMed search (restricted from 1/1/90 to 8/25/00) using keywords related to physical activity, physical fitness, and health. An author scanned titles and abstracts of 9831 identified articles. We included for thorough review articles that included three or more categories of activity or fitness and a health outcome and excluded articles on clinical trials, review papers, comments, letters, case reports, and nonhuman studies. We used an evidence-based approach to evaluate the quality of the published data. We summarized results from 67 articles meeting final selection criteria. There is good consensus across studies with most showing an inverse dose-response gradient across both activity and fitness categories for morbidity from coronary heart disease (CHD), stroke, cardiovascular disease (CVD), or cancer; and for CVD, cancer, or all-cause mortality. All studies reviewed were prospective observational investigations; thus, conclusions are based on Evidence Category C. 1) There is a consistent gradient across activity groups indicating greater longevity and reduced risk of CHD, CVD, stroke, and colon cancer in more active individuals. 2) Studies are compelling in the consistency and steepness of the gradient across fitness groups. Most show a curvilinear gradient, with a steep slope at low levels of fitness and an asymptote in the upper part of the fitness distribution. 3) It is not possible to conclude whether activity or fitness is more important for health. Future studies should define more precisely the shape of the dose-response gradient across activity or fitness groups, evaluate the role of musculoskeletal fitness, and investigate additional health outcomes.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                19 June 2019
                June 2019
                : 20
                : 12
                : 2999
                Affiliations
                [1 ]Molecular Toxicology Group, Department of Biology, Box 628, University of Konstanz, 78457 Konstanz, Germany; tabea.hammes@ 123456uni-konstanz.de (T.H.); alexander.buerkle@ 123456uni-konstanz.de (A.B.)
                [2 ]Human Performance Research Centre, Department of Sport Science, Box 30, University of Konstanz, 78457 Konstanz, Germany; andreas.kramer@ 123456uni-konstanz.de (A.K.); maria.venegas@ 123456uni-konstanz.de (M.V.-C.); p4trickthumm@ 123456gmail.com (P.T.); m.gruber@ 123456uni-konstanz.de (M.G.)
                Author notes
                [* ]Correspondence: maria.moreno-villanueva@ 123456uni-konstanz.de ; Tel.: +49-7531-88-3599
                [†]

                Shared first authorship.

                [‡]

                Shared last authorship.

                Author information
                https://orcid.org/0000-0002-2586-5508
                https://orcid.org/0000-0003-1069-2656
                https://orcid.org/0000-0002-0233-3912
                Article
                ijms-20-02999
                10.3390/ijms20122999
                6628277
                31248182
                cb859113-b81e-4c0f-a257-a34c92dae198
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2019
                : 10 June 2019
                Categories
                Communication

                Molecular biology
                aerobic fitness,endurance exercise,dna strand breaks,radiation protection,parp1 activity

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