Involvement of oxidative modification of proteins related to ATP synthesis in the left ventricles of hamsters with cardiomyopathy

Abstract

Inflammation enhanced by accumulation of reactive oxygen species plays an essential role in the progression of cardiovascular diseases. Using the 2D-oxyblot analysis and 2D-difference image gel electrophoresis (2D-DIGE), we compared the levels of ROS-induced carbonyl modification of myocardial proteins in the whole left ventricles between 6-week-old hamsters with dilated (TO-2) and hypertrophic cardiomyopathy (Bio14.6) and control hamsters (F1B). Then, 2D electrophoresis combined with MALDI-TOF/TOF tandem mass spectrometry detected 18 proteins with increased carbonyl level in cardiomyopathy hamsters compared with control hamster. Carbonyl modification of proteins related to ATP synthesis, including citric acid cycle and electron transport system, was observed in the hearts of hamsters with both types of cardiomyopathy. Further analysis indicated that left ventricular carbonyl production correlated negatively with succinyl-CoA:3-ketoacid-coenzyme A transferase 1 activity (r 2 = 0.60, P = 0.0007) and ATP concentration (r 2 = 0.29, P = 0.037), suggesting that protein carbonylation has negative effects on the levels of these biomolecules. Furthermore, carbonyl production significantly correlated with plasma Troponin T level (r 2 = 0.33, P = 0.026). Reduction of energy metabolism by oxidative damage may contribute to the development of left ventricular impairment in cardiomyopathy.

Enhanced Catecholamine Flux and Impaired Carbonyl Metabolism Disrupt Cardiac Mitochondrial Oxidative Phosphorylation in Diabetes Patients

“…Since the effect of NE was mitigated by MAO inhibitors, it is most likely due to the reactivity of MAO-derived byproducts. Numerous oxidative post-translational modifications of the ATP synthase have been reported to affect ATP synthase efficiency (32,62,65). Using the APBA resin to pull down catechol-modified proteins, our proteomic analysis confirmed that multiple isoforms of ANT and ATP-synthase are, indeed, potential targets of catecholaldehydes (Fig.…”

Cardioprotective effects of α‐cardiac actin on oxidative stress in a dilated cardiomyopathy mouse model

“…This protective effect has been already described in budding yeast in which the capacity to survive elevated oxidative stress is sensitive to cytoplasmic actin dynamics though the exact process involved is still unknown . Under pathological conditions, several sources of ROS lead to deleterious oxidative stress in the cardiac muscle, such as mitochondrial respiratory chain dysfunction and monooxygenase enzymes . So, is α‐cardiac actin able to reduce oxidative stress by impacting on these sources of ROS?…”

“…53,54 Under pathological conditions, several sources of ROS lead to deleterious oxidative stress in the cardiac muscle, such as mitochondrial respiratory chain dysfunction and monooxygenase enzymes. [55][56][57][58] So, is α-cardiac actin able to reduce oxidative stress by impacting on these sources of ROS? At first, we demonstrated that maintaining α-cardiac actin preserves the alignment of mitochondrial network and the global aspect of these organelles.…”

Functional Redox Proteomics Reveal That Salvia miltiorrhiza Aqueous Extract Alleviates Adriamycin-Induced Cardiomyopathy via Inhibiting ROS-Dependent Apoptosis

“…It is well-established that biomolecule oxidation is closely linked to a series of pathological events; the accumulation of redox-dependent posttranslational modification of certain key proteins would lead to ER stress and subsequent activation of the mitochondrial apoptotic pathway. The heart is one of the highest ATP-consuming organs and most of ATP is generated by the mitochondria through primarily oxidative phosphorylation [ 34 – 38 ]. Furthermore, network analysis has suggested that ADR-caused heart damage is majorly caused by impaired protein folding due to oxidative stress and mitochondrial dysfunction.…”