title: Calpeptin attenuated apoptosis and intracellular inflammatory changes in muscle cells.
abstract: In idiopathic inflammatory myopathies (IIMs), extracellular inflammatory stimulation is considered to induce secondary intracellular inflammatory changes including expression of major histocompatibility complex class-I (MHC-I) and to produce a self-sustaining loop of inflammation. We hypothesize that activation of calpain, a Ca(2+) -sensitive protease, bridges between these extracellular inflammatory stress and intracellular secondary inflammatory changes in muscle cells. In this study, we demonstrated that treatment of rat L6 myoblast cells with interferon-γ (IFN-γ) caused expression of MHC-I and inflammation-related transcription factors (phosphorylated-extracellular signal-regulated kinase 1/2 and nuclear factor-κB). We also demonstrated that treatment with tumor necrosis factor-α (TNF-α) induced apoptotic changes and activation of calpain and cyclooxygenase-2. Furthermore, we found that posttreatment with calpeptin attenuated the intracellular changes induced by IFN-γ or TNF-α. Our results indicate that calpain inhibition attenuates apoptosis and secondary inflammatory changes induced by extracellular inflammatory stimulation in the muscle cells. These results suggest calpain as a potential therapeutic target for treatment of IIMs.
authors.affiliation: Division of Neurology, Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Nozaki
authors.forename: Arabinda
authors.initials: A
authors.lastname: Das
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015153:Blotting, Western; D002154:Calpain / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000276:immunology / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009220:Myositis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C071482:calpeptin; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D002154:Calpain