{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:35:22Z","timestamp":1790174122535,"version":"4.1.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:p>Calpain activation has been implicated in the disease pathology of Duchenne muscular dystrophy. Inhibition of calpain has been proposed as a promising therapeutic target, which could lessen the protein degradation and prevent progressive fibrosis. At the same time, there are conflicting reports as to whether elevation of calpastatin, an endogenous calpain inhibitor, alters pathology. We compared the effects of pharmacological calpain inhibition in the mdx mouse using leupeptin and a proprietary compound (C101) that linked the inhibitory portion of leupeptin to carnitine (to increase uptake into muscle). Administration of C101 for 4 wk did not improve muscle histology, function, or serum creatine kinase levels in mdx mice. Mdx mice injected daily with leupeptin (36 mg\/kg) for 6 mo also failed to show improved muscle function, histology, or creatine kinase levels. Biochemical analysis revealed that leupeptin administration caused an increase in m-calpain autolysis and proteasome activity, yet calpastatin levels were similar between treated and untreated mdx mice. These data demonstrate that pharmacological inhibition of calpain is not a promising intervention for the treatment of Duchenne muscular dystrophy due to the ability of skeletal muscle to counter calpain inhibitors by increasing multiple degradative pathways.<\/jats:p>","DOI":"10.1152\/ajpregu.00586.2009","type":"journal-article","created":{"date-parts":[[2010,9,16]],"date-time":"2010-09-16T02:40:01Z","timestamp":1284604801000},"page":"R1192-R1201","source":"Crossref","is-referenced-by-count":32,"title":["Leupeptin-based inhibitors do not improve the mdx phenotype"],"prefix":"10.1152","volume":"299","author":[{"given":"Joshua","family":"Selsby","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Pendrak","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zadel","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and"},{"name":"Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuozhen","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Pham","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted","family":"Carver","sequence":"additional","affiliation":[{"name":"CepTor Corporation, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Barton","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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