Circulating E3 ligases are novel and sensitive biomarkers for diagnosis of acute myocardial infarction.

Ubiquitin ligase (E3) is a decisive element of the ubiquitin-proteasome system (UPS), which is the main pathway for intracellular protein turnover. Recently, circulating E3 ligases have been increasingly considered as cancer biomarkers. In the present study, we aimed to determine if cardiac-specific E3 ligases in circulation can serve as novel predictors for early diagnosis of acute myocardial infarction (AMI). By screening and verifying their tissue expression patterns with microarray and real-time PCR analysis, six of 261 E3 ligases, including cardiac-specific Rnf207 and cardiac- and muscle-enriched Fbxo32/atrogin-1, Trim54/MuRF3, Trim63/MuRF1, Kbtbd10/KLHL41, Asb11 and Asb2 in mouse heart, were selected for the present study. In the AMI rats, the levels of five E3 ligases including Rnf207, Fbxo32, Trim54, Trim63 and Kbtbd10 in the plasma were significantly increased compared with control animals. Especially, the plasma levels of Rnf207 was markedly increased at 1 h, peaked at 3 h and decreased at 6-24 h after ligation. Further evaluation of E3 ligases in AMI patients confirmed that plasma Rnf207 level increased significantly compared with that in healthy people and patients without AMI, and showed a similar time course to that in AMI rats. Simultaneously, plasma level of cardiac troponin I (cTnI) was measured by ELISA assays. Finally, receiver operating characteristic (ROC) curve analysis indicated that Rnf207 showed a similar sensitivity and specificity to the classic biomarker troponin I for diagnosis of AMI. Increased cardiac-specific E3 ligase Rnf207 in plasma may be a novel and sensitive biomarkers for AMI in humans.

Effects of age on serum hormone concentrations and intramuscular proteolytic signaling before and after a single bout of resistance training.

This study examined mRNA expression patterns for atrogin-1 and muscle ring finger-1 (MuRF-1) before and 24 hours after a resistance training bout. Furthermore, basal, 5-minute and 24-hour postexercise serum concentrations of cortisol and insulin like growth factor-1 (IGF-1) and the relationships between these hormones and the genetic expression patterns of atrogin-1 and MuRF-1 were examined. Younger and older men completed a resistance exercise bout consisting of 3 × 10 repetitions at 80% of their predetermined 1 repetition maximum for Smith squat, leg press and leg extension. Muscle biopsies from the vastus lateralis were obtained before and 24 hours after exercise. Basal and postexercise gene expression differences between age groups were analyzed using the Mann-Whitney U test, whereas separate 2 × 3 repeated measures analyses of variance were performed to analyze changes in hormone concentrations. Spearman's correlations were performed to examine relationships between gene expression patterns and hormone concentrations. Serum cortisol was significantly greater in younger men before and 24 hours after exercise (p < 0.05), whereas serum IGF-1 was significantly greater in younger men at all time points (p < 0.001). Exercise significantly increased cortisol 5 minutes after exercise in both groups (p < 0.05), whereas older men experienced significant elevations in IGF-1 24 hours postexercise (p < 0.05). At baseline, MuRF-1 gene expression was significantly greater in older men (p = 0.03), whereas no age-related differences were found for atrogin-1 (p = 0.24). Fold change in atrogin-1 and MuRF-1 24 hours postexercise revealed no significant differences between younger and older men. Differential baseline expression of MuRF-1 may suggest a regulatory attempt by the aging transcriptome to accommodate changes necessary for homeostatic maintenance. An enhanced understanding of molecular and genetic level adaptations can aid researchers in developing optimal therapeutic and exercise interventions to mitigate decrements in force, power, and loss of muscle mass seen in aging and many clinical populations.