دورية أكاديمية
A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress.
العنوان: | A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress. |
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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.) |
References: | J Biol Chem. 1974 Aug 25;249(16):5337-45. (PMID: 4152841) PLoS One. 2012;7(7):e41817. (PMID: 22848618) J Appl Physiol (1985). 2007 Apr;102(4):1677-86. (PMID: 17095633) J Biol Chem. 2007 Oct 12;282(41):30014-21. (PMID: 17702743) Mol Cell. 1998 Nov;2(5):559-69. (PMID: 9844629) Oxid Med Cell Longev. 2012;2012:756132. (PMID: 22701757) Annu Rev Physiol. 2019 Feb 10;81:19-41. (PMID: 30216742) J Cell Sci. 2017 Aug 1;130(15):2551-2563. (PMID: 28600325) BMC Musculoskelet Disord. 2012 Nov 08;13:218. (PMID: 23136874) Sports Med. 2019 Apr;49(4):509-523. (PMID: 30778851) Nat Rev Mol Cell Biol. 2015 Sep;16(9):519-32. (PMID: 26296162) Circulation. 1970 Oct;42(4):611-24. (PMID: 11993304) J Exp Biol. 2014 Jun 1;217(Pt 11):1993-2003. (PMID: 24625643) Cell Metab. 2015 Feb 3;21(2):237-248. (PMID: 25651178) Am J Physiol Cell Physiol. 2009 Jun;296(6):C1245-7. (PMID: 19357232) Diabetes. 2012 Dec;61(12):3322-32. (PMID: 23028138) Drug Discov Today. 2014 Jul;19(7):1010-4. (PMID: 24631681) Biomolecules. 2015 Apr 10;5(2):356-77. (PMID: 25866921) Oxid Med Cell Longev. 2019 Jun 19;2019:7058350. (PMID: 31320983) Nat Genet. 2011 Dec 04;44(1):23-31. (PMID: 22138693) Compr Physiol. 2011 Apr;1(2):941-69. (PMID: 23737208) Exp Mol Med. 2016 Nov 25;48(11):e272. (PMID: 27885254) Nat Med. 2015 Mar;21(3):281-7. (PMID: 25706873) J Biol Chem. 2014 Mar 21;289(12):8106-20. (PMID: 24482226) Front Physiol. 2016 Oct 06;7:446. (PMID: 27766080) J Endocrinol. 2017 Apr;233(1):R15-R42. (PMID: 28232636) Science. 2011 Sep 9;333(6048):1440-5. (PMID: 21903813) Chem Biol Interact. 2019 Apr 1;302:149-155. (PMID: 30794800) Genome Biol. 2014;15(12):550. (PMID: 25516281) Physiology (Bethesda). 2015 Jan;30(1):30-9. (PMID: 25559153) Oxid Med Cell Longev. 2016;2016:1245049. (PMID: 27478531) Sci Data. 2018 Oct 30;5:180213. (PMID: 30375987) Nat Commun. 2019 Oct 11;10(1):4623. (PMID: 31604916) Br J Sports Med. 2015 Dec;49(24):1567-78. (PMID: 25824446) Front Physiol. 2016 Nov 07;7:486. (PMID: 27872595) Cell Physiol Biochem. 2017;44(1):314-332. (PMID: 29132139) Antioxid Redox Signal. 2013 Apr 1;18(10):1208-46. (PMID: 22978553) EMBO J. 2021 May 3;40(9):e106491. (PMID: 33847380) Oncotarget. 2018 Mar 30;9(24):17181-17198. (PMID: 29682215) J Exerc Rehabil. 2018 Aug 24;14(4):551-558. (PMID: 30276173) Redox Biol. 2020 Aug;35:101477. (PMID: 32127290) Oncotarget. 2016 Aug 9;7(32):50814-50815. (PMID: 27449104) Am J Physiol Endocrinol Metab. 2015 May 15;308(10):E912-20. (PMID: 25805191) J Appl Physiol (1985). 2015 Sep 15;119(6):643-55. (PMID: 26112242) J Biol Chem. 2006 Sep 8;281(36):26473-82. (PMID: 16762927) Biochim Biophys Acta. 2004 Jun 28;1657(1):1-22. (PMID: 15238208) Cell. 1999 Nov 24;99(5):451-4. (PMID: 10589672) Expert Opin Ther Targets. 2019 Feb;23(2):153-160. (PMID: 30580640) Genes Cancer. 2011 Feb;2(2):130-9. (PMID: 21779486) Nat Genet. 2003 Mar;33 Suppl:245-54. (PMID: 12610534) Cell Metab. 2007 Jan;5(1):35-46. (PMID: 17189205) Free Radic Biol Med. 2016 Sep;98:18-28. (PMID: 27184955) Cell Metab. 2012 Mar 7;15(3):405-11. (PMID: 22405075) Antioxid Redox Signal. 2013 Feb 20;18(6):603-21. (PMID: 23050834) Br J Pharmacol. 2017 Jun;174(12):1670-1689. (PMID: 26660451) Cell. 2014 Nov 6;159(4):738-49. (PMID: 25417152) J Biol Chem. 2011 Mar 25;286(12):10605-17. (PMID: 21245132) Cell Metab. 2010 Dec 1;12(6):633-42. (PMID: 21109195) Free Radic Biol Med. 2011 Jul 15;51(2):417-23. (PMID: 21569841) Molecules. 2013 Mar 01;18(3):2821-39. (PMID: 23455672) Redox Biol. 2015 Dec;6:472-485. (PMID: 26432659) Nat Methods. 2015 Apr;12(4):357-60. (PMID: 25751142) Wiley Interdiscip Rev Dev Biol. 2016 Jul;5(4):518-34. (PMID: 27199166) Int J Biochem Cell Biol. 2014 May;50:101-5. (PMID: 24582887) Redox Biol. 2015 Dec;6:260-271. (PMID: 26296072) Microcirculation. 2006 Apr-May;13(3):175-86. (PMID: 16627360) Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):897-906. (PMID: 20122895) Chem Biol Interact. 2009 Mar 16;178(1-3):84-93. (PMID: 18848533) PLoS One. 2014 Aug 14;9(8):e103044. (PMID: 25121500) Cell Metab. 2018 Oct 2;28(4):631-643.e3. (PMID: 30078553) Cell Mol Immunol. 2015 Jan;12(1):5-23. (PMID: 25263488) Semin Cell Dev Biol. 2018 Oct;82:51-56. (PMID: 29241690) Oxid Med Cell Longev. 2017;2017:3165396. (PMID: 28656072) Dev Dyn. 2007 Jun;236(6):1663-76. (PMID: 17477386) Front Cell Dev Biol. 2018 Sep 28;6:125. (PMID: 30324104) J Mol Cell Biol. 2019 Feb 1;11(2):133-143. (PMID: 30428023) Histochem J. 1989 Sep-Oct;21(9-10):545-55. (PMID: 2556354) J Cachexia Sarcopenia Muscle. 2015 Sep;6(3):197-207. (PMID: 26401465) Exerc Sport Sci Rev. 2014 Oct;42(4):169-74. (PMID: 25062000) |
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 |
تدمد: | 1460-2075 |
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DOI: | 10.15252/embj.2020106491 |