Reactive γ-ketoaldehydes promote protein misfolding and preamyloid oligomer formation in rapidly-activated atrial cells》.pdf

Journal of Molecular and Cellular Cardiology 79 (2015) 295 –302 Contents lists available at ScienceDirect Journal of Molecular and Cellular Cardiology journal homepage: /locate/yjmcc Original article Reactive γ-ketoaldehydes promote protein misfolding and preamyloid oligomer formation in rapidly-activated atrial cells Tatiana N. Sidorova a, Liudmila V. Yermalitskaya a, Lisa C. Mace a, K. Sam Wells b, Olivier Boutaud a, Joseph K. Prinsen a, Sean S. Davies a, L. Jackson Roberts II a, Sergey I. Dikalov a, Charles G. Glabe d, Venkataraman Amarnath c, Joey V. Barnett a, Katherine T. Murray a,⁎ a Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA b Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA c Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA d University of California, Irvine, Irvine, CA, USA a r t i c l e i n f o a b s t r a c t Article history: Rapid activation causes remodeling of atrial myocytes resembling that which occurs in experimental and human Received 22 August 2014 atrial fibrillation (AF). Using this cellular model, we previously observed transcriptional upregulation of proteins Received in revised form 24 October 2014 implicated in protein misfolding and amyloidosis. For organ-specific amyloidoses such as Alzheimers disease, Accepted 12 November 2014 preamyloid oligomers (PAOs) are now recognized to be the primary cytotoxic species.