The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts

Oxidative stress is defined as an imbalance between the antioxidant defense system and production of reactive oxygen species (ROS). At low levels, ROS are involved in regulation redox signaling for cell protection. However, upon chronical increase oxidative stress, damage occurs, due to protein, DNA lipid oxidation. Here, we investigated modifications myofilament proteins, their role modulating cardiomyocyte function end-stage human failing hearts. We found altered maximum Ca2+-activated tension Ca2+ sensitivity force skinned single cardiomyocytes hearts compared non-failing hearts, which was corrected treatment with reduced glutathione enzyme. This accompanied by increased oxidation troponin I myosin binding protein C, decreased levels kinases A (PKA)- C (PKC)-mediated phosphorylation both proteins. The maximal correlated strongly hypo-phosphorylation, parameters that were measured all samples. Furthermore, detected elevated titin-based myocardial stiffness HF myocytes, reversed PKA enzyme treatment. Finally, many inflammation significantly anti-oxidant GSH provide evidence mechanical properties partially phosphorylation, S-glutathionylation, interplay two post-translational modifications, contribute development heart failure.