Abstract
Many models of oxidative stress lead to heart failure syndromes that are not associated with changes in Ca2+-homeostasis, and are likely attributable to oxidative stress-dependent modifications of sarcomeric proteins. Yet, the possible sarcomeric targets and specific modifications are poorly understood. In the present study, we evaluate whether cardiac sarcomeric proteins manifest different sensitivities to metal (iron) catalyzed oxidative stress. Exposure of rat myocytes to H2O2 lead to the production of: i) myofilament-protein aggregates resistant to reducing (DTT) and denaturing (urea/thiourea) conditions; and ii) myofilament breakdown, even in the presence of cell permeable protease inhibitors. Pre-incubation of myocytes with cell-permeable metal chelators (like desferoxamine) completely abolished myofilament breakdown and aggregation. Similar myofilament-protein aggregates were detected in failing rat and human myocardium. Isolated rat ventricular myofibrils exposed to H2O2 and iron (Fe2+) closely recapitulate cellular results. Dose dependent experiments reveal that most sarcomeric phosphoproteins undergo dephosphorylation and breakdown at lower oxidative stress levels compared with non-phosphoproteins.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
