REGULATION OF THE CALPAIN AND UBIQUITIN-PROTEASOME SYSTEMS IN A CANINE MODEL OF MUSCULAR DYSTROPHY

Introduction: Previous studies have tested the hypothesis that calpain and/or proteasome inhibition is beneficial in Duchenne muscular dystrophy, based largely on evidence that calpain and proteasome activities are enhanced in the mdx mouse. Methods: mRNA expression of ubiquitin-proteasome and calpain system components were determined using real-time polymerase chain reaction in skeletal muscle and heart in the golden retriever muscular dystrophy model. Similarly, calpain 1 and 2 and proteasome activities were determined using fluorometric activity assays. Results: We found that less than half of the muscles tested had increases in proteasome activity, and only half had increased calpain activity. In addition, transcriptional regulation of the ubiquitin-proteasome system was most pronounced in the heart, where numerous components were significantly decreased. Conclusion: This study illustrates the diversity of expression and activities of the ubiquitin-proteasome and calpain systems, which may lead to unexpected consequences in response to pharmacological inhibition. Muscle Nerve 44: 553-562, 2011