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:Cardiac cachexia (CC) is an advanced stage of heart failure (HF) characterized by structural and functional abnormalities in skeletal muscle, leading to muscle loss. Aerobic training provides benefits; however, the underlying molecular mechanisms remain poorly understood. This study aimed to investigate the therapeutic effects of aerobic training on transcriptomic alterations associated with disease progression in cachectic skeletal muscle. HF was induced in male Wistar rats by a single monocrotaline injection (60mg/Kg). Aerobic training consisted of treadmill running for 30min at ~55% of maximal capacity, 5x/week for 4 weeks. Assessments included body mass, right ventricle mass, skeletal muscle fiber size and exercise tolerance. RNA sequencing analysis was per-formed on the medial gastrocnemius muscle. Sedentary cachectic rats exhibited 114 differentially expressed genes (DEGs) while exercised cachectic rats had only 18 DEGs compared to their respective controls. GO enrichment, pathway enrichment, and weighted gene co-expression network analysis (WGCNA) identified key DEGs as po-tential hub genes involved in disrupted lipid metabolism and muscle remodeling in sedentary CC rats, which were not observed in the exercised CC rats. These findings suggest that aerobic training mitigates transcriptional alterations related to lipid me-tabolism and muscle remodeling in rats with CC, highlighting its therapeutic potential.