Abstract
OBJECTIVE: In skeletal muscle, glucocorticoids induce catabolism and proteolysis which is accomplished via the ubiquitin (Ub) proteolytic pathway. Cardiac muscle is a striated muscle which, compared to skeletal muscle, more abundantly expresses components of the Ub pathway, thus suggesting an important role for this pathway in heart physiology. The aim of our study was to explore the role of the Ub pathway in heart muscle physiology. DESIGN: We treated rats for three days with a pharmacologic dose of dexamethasone (DEXA) 0.5mg/100g body weight (BW). An attempt was also made to counteract the DEXA effect by co-treatment with insulinlike growth factor-1 (IGF-1; 0.35mg/100g BW). RESULTS: DEXA treatment caused a 7.8% decrease in heart weight compared to control (p<0.05) and also increased heart tissue levels of the ubiquitin-conjugating enzyme E2 and the 20S proteasome protein. Myofibrillar proteins degraded by the ubiquitin pathway (α-actin, myoglobin, and troponin 1) were all decreased by DEXA, while ubiquitinated forms of α-actin were increased. Co-treatment with IGF-1 completely prevented DEXA-induced decrease in heart weight, an effect which was accompanied by decreased heart tissue levels of several ubiquitinated proteins including α-actin, the 20S proteasome protein, E2-14kDa mRNA, and C-3 proteasome subunit mRNA, while the levels of non-ubiquinated α-actin, myoglobin, and troponin 1 were all partially restored. CONCLUSION: These results demonstrate that DEXA activates the ubiquitin proteolytic pathway in the heart and that IGF-1 efficiently counteracts this effect. Our findings reveal a possible mechanism for the anti-proteolytic actions of IGF-1 and its cardioprotective role involving the Ub pathway.
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Chrysis, D., Chagin, A.S. & Sävendahl, L. Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway. Hormones 10, 46–56 (2011). https://doi.org/10.14310/horm.2002.1292
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DOI: https://doi.org/10.14310/horm.2002.1292