Project description:Oxidative posttranslational modifications (Ox-PTMs) regulate cellular homeostasis in several tissues, including skeletal and cardiac muscles. The putative relationship between Ox-PTMs and intrinsic components of oxidative energy metabolism has not been previously described. We determined the metabolic phenotype and the Ox-PTM profile in the skeletal and cardiac muscles of rats selected for low (LCR) or high (HCR) intrinsic aerobic capacity. The HCR rats have a pronounced increase in mitochondrial content and antioxidant capacity when compared to LCR rats in the skeletal muscle, but only modest changes in the cardiac muscle. Redox proteomics analysis reveals that HCR and LCR rats have different Ox-PTM of cysteine (Cys) residue profile in the skeletal and cardiac muscles. HCR rats have higher number of oxidized Cys residues in the skeletal muscle and conversely display higher number of reduced Cys residues in the cardiac muscle than LCR rats. Most of the proteins with differentially oxidized Cys residues in the skeletal muscle are important regulators of the oxidative metabolism. The most significantly oxidized protein in the skeletal muscle of HCR rats is malate dehydrogenase (MDH1). Interestingly, HCR rats show higher MDH1 activity in the skeletal muscle, but not in the cardiac muscle. Thus, this study uncovers an association between Ox-PTMs and intrinsic aerobic capacity, providing new insights into the role of Ox-PTMs as essential signaling to maintain metabolic homeostasis in different muscle types.
Project description:Rosiglitazone, a peroxisome proliferator-activated receptor g (PPARg) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone. Male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone once per day for 14 days. Samples were obtained 6, 24, 168 or 336 hours after the final treatment.