Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis

• DOI: 10.1172/jci.insight.126347
• Publication Date: 2019-03-28T16:01:02Z
• Authors: Maarten M. Steinz; Malin Persson; Bejan Aresh; Karl Olsson; Arthur J. Cheng; Emma Ahlstrand; Mats Lilja; Tommy R. Lundberg; Eric Rullman; Kristina Ängeby M...; Katalin Sandor; Sofia Ajeganova; Takashi Yamada; Nicole Beard; Björn C.G. Karlsson; Pasi Tavi; Ellinor Kenne; Camilla I. Svensson; Dilson E. Rassier; Roger Karlsson; Ran Friedman; Thomas Gustafsson; Johanna T. Lanner
• Keywords: Muscle weakness

Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on associated with RA. Oxidative stress has been implicated the disease pathogenesis Here we show that oxidative post-translational modifications contractile machinery targeted actin result polymerization force production. Using mass spectrometry, identified residues by 3-nitrotyrosine (3-NT) or malondialdehyde adduct (MDA) weakened skeletal mice afflicted The were primarily located three distinct regions positioned at matching surface areas molecule RA patients. Moreover, dynamic simulations revealed these areas, here coined "hotspots", are important for stability its capacity generate filaments interact myosin. Together, data demonstrate how promote provide novel leads therapeutic treatment improve function.