دورية أكاديمية
أعرض في EDS

A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress.

التفاصيل البيبلوغرافية
العنوان: A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress.
المؤلفون: Damal Villivalam S; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., Ebert SM; Departments of Internal Medicine and Molecular Physiology and Biophysics and Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.; Emmyon, Inc., Coralville, IA, USA., Lim HW; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics & Biomedical Informatics, University of Cincinnati, Cincinnati, OH, USA., Kim J; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., You D; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., Jung BC; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., Palacios HH; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., Tcheau T; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA., Adams CM; Departments of Internal Medicine and Molecular Physiology and Biophysics and Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.; Emmyon, Inc., Coralville, IA, USA.; Iowa City Department of Veterans Affairs Medical Center, Iowa City, IA, USA., Kang S; Nutritional Sciences and Toxicology Department, University of California Berkeley, Berkeley, CA, USA.
المصدر: The EMBO journal [EMBO J] 2021 May 03; Vol. 40 (9), pp. e106491. Date of Electronic Publication: 2021 Apr 13.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
مواضيع طبية MeSH: DNA (Cytosine-5-)-Methyltransferases/*genetics , Muscle, Skeletal/*metabolism , Oxidoreductases Acting on CH-NH Group Donors/*genetics , Physical Endurance/*genetics, Animals ; Cell Line ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methyltransferase 3A ; Gene Expression Profiling ; Gene Knockout Techniques ; Mice ; Mitochondria, Muscle/metabolism ; Oxidative Stress ; Oxidoreductases Acting on CH-NH Group Donors/metabolism ; Rats ; Reactive Oxygen Species/metabolism ; Sequence Analysis, RNA
مستخلص: Exercise can alter the skeletal muscle DNA methylome, yet little is known about the role of the DNA methylation machinery in exercise capacity. Here, we show that DNMT3A expression in oxidative red muscle increases greatly following a bout of endurance exercise. Muscle-specific Dnmt3a knockout mice have reduced tolerance to endurance exercise, accompanied by reduction in oxidative capacity and mitochondrial respiration. Moreover, Dnmt3a-deficient muscle overproduces reactive oxygen species (ROS), the major contributors to muscle dysfunction. Mechanistically, we show that DNMT3A suppresses the Aldh1l1 transcription by binding to its promoter region, altering its epigenetic profile. Forced expression of ALDH1L1 elevates NADPH levels, which results in overproduction of ROS by the action of NADPH oxidase complex, ultimately resulting in mitochondrial defects in myotubes. Thus, inhibition of ALDH1L1 pathway can rescue oxidative stress and mitochondrial dysfunction from Dnmt3a deficiency in myotubes. Finally, we show that in vivo knockdown of Aldh1l1 largely rescues exercise intolerance in Dnmt3a-deficient mice. Together, we establish that DNMT3A in skeletal muscle plays a pivotal role in endurance exercise by controlling intracellular oxidative stress.
(© 2021 The Authors.)
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معلومات مُعتمدة: I01 BX000976 United States BX BLRD VA; R01 AG060637 United States AG NIA NIH HHS; R01 AR071762 United States AR NIAMS NIH HHS; R01 DK116008 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: DNA methylation; exercise; oxidative stress
سلسلة جزيئية: GEO GSE159105
المشرفين على المادة: 0 (Dnmt3a protein, mouse)
0 (Reactive Oxygen Species)
EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
EC 1.5.1.6 (formyltetrahydrofolate dehydrogenase)
EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
EC 2.1.1.37 (DNA Methyltransferase 3A)
تواريخ الأحداث: Date Created: 20210413 Date Completed: 20211104 Latest Revision: 20220506
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8090849
DOI: 10.15252/embj.2020106491
PMID: 33847380
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2075
DOI:10.15252/embj.2020106491