Alterations of redox dynamics and desmin post-translational modifications in skeletal muscle models of desminopathies

Experimental Cell Research
Florence DelortSabrina Batonnet-Pichon

Abstract

Desminopathies are a type of myofibrillar myopathy resulting from mutations in DES, encoding the intermediate filament protein desmin. They display heterogeneous phenotypes, suggesting environment influences. Patient muscle proteins show oxidative features linking oxidative stress, protein aggregation, and abnormal protein deposition. To improve understanding of redox balance in desminopathies, we further developed cellular models of four pathological mutants localized in 2B helical domain (the most important region for desmin polymerization) to explore desmin behavior upon oxidative stress. We show that the mutations desQ389P and desD399Y share common stress-induced aggregates, desR406W presents more scattered cytoplasmic aggregative pattern, and pretreatment with N-acetyl-l-cysteine (NAC), an antioxidant molecule, prevents all type of aggregation. Mutants desD399Y and desR406W had delayed oxidation kinetics following H2O2 stress prevented by NAC pretreatment. Further, we used AAV-injected mouse models to confirm in vivo effects of N-acetyl-l-cysteine. AAV-desD399Y-injected muscles displayed similar physio-pathological characteristics as observed in patients. However, after 2 months of NAC treatment, they did not have reduced ...Continue Reading

References

Mar 20, 1991·Journal of Molecular Biology·M W MacArthur, J M Thornton
Jan 1, 1985·Annals of the New York Academy of Sciences·K Weber, N Geisler
Apr 25, 1988·FEBS Letters·L RappaportM Fardeau
Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·P M SteinertR D Goldman
May 1, 1996·Developmental Biology·Z LiC Babinet
Sep 1, 1996·The Journal of Cell Biology·D J MilnerY Capetanaki
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Kathleen A ClarkCarol C Gregorio
Feb 22, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Sergei V StrelkovUeli Aebi
Mar 1, 2003·Neuromuscular Disorders : NMD·Marinos C DalakasLev G Goldfarb
Oct 13, 2004·Journal of Structural Biology·Harald BärHarald Herrmann
Oct 12, 2005·Proceedings of the National Academy of Sciences of the United States of America·Harald BärHarald Herrmann
Mar 24, 2006·Nature Methods·Vsevolod V BelousovSergey Lukyanov
Jul 26, 2006·Human Mutation·Bertrand GoudeauPatrick Vicart
Aug 8, 2006·International Journal of Cardiology·Piotr PruszczykAnna Kamiñska
Nov 16, 2006·Journal of Cell Science·Karine LapougeLuca Borradori
Apr 10, 2007·Neuromuscular Disorders : NMD·Montse OlivéIsidre Ferrer
Sep 21, 2007·Journal of Neuropathology and Experimental Neurology·Anna JanuéIsidro Ferrer
Jan 15, 2008·Free Radical Biology & Medicine·Zsolt RadakSataro Goto
May 13, 2008·Nature Methods·Marcus GutscherTobias P Dick
Jun 20, 2008·Journal of Muscle Research and Cell Motility·Anna KostarevaThomas Sejersen
Nov 11, 2010·The Journal of Biological Chemistry·Natasha T SniderM Bishr Omary
Jan 26, 2011·Experimental Cell Research·Oussama ChourbagiOnnik Agbulut
Aug 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Anastasia A ChernyatinaSergei V Strelkov
Nov 13, 2012·Acta Neuropathologica·Christoph S ClemenRolf Schröder
Oct 8, 2013·PloS One·Bertrand-David SegardSabrina Batonnet-Pichon
Feb 4, 2014·The Journal of Clinical Investigation·Lilli WinterGerhard Wiche
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Natasha T Snider, M Bishr Omary
Sep 19, 2015·Electrophoresis·Matteo MariniGaetano Vattemi
Dec 8, 2015·The Journal of Physiology·Troy L Merry, Michael Ristow
Feb 20, 2016·The Journal of Physiology·Scott K PowersLi Li Ji

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