Abstract:
:Idiopathic inflammatory myopathies (IIMs), comprising of polymyositis, dermatomyositis, and inclusion-body myositis, are characterized by muscle weakness and various types of inflammatory changes in muscle cells. They also show non-inflammatory changes, including perifascicular atrophy, mitochondrial changes, and amyloid protein accumulation. It is possible that some molecules/mechanisms bridge the extracellular inflammatory stimulation and intracellular non-inflammatory changes. One such mechanism, Ca(2+) influx leading to calpain activation has been proposed. In this study, we demonstrated that post-treatment with calpeptin (calpain inhibitor) attenuated intracellular changes to prevent apoptosis (Wright staining) through both mitochondrial pathway (increase in Bax:Bcl-2 ratio) and endoplasmic reticulum stress pathway (activation of caspase-12), which were induced by interferon-gamma (IFN-γ) stimulation in rat L6 myoblast cells. Our results also showed that calpeptin treatment inhibited the expression of calpain, aspartyl protease cathepsin D, and amyloid precursor protein. Thus, our results indicate that calpain inhibition plays a pivotal role in attenuating muscle cell damage from inflammatory stimulation due to IFN-γ, and this may suggest calpain as a possible therapeutic target in IIMs.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Nozaki K,Das A,Ray SK,Banik NLdoi
10.1016/j.expneurol.2010.07.021subject
Has Abstractpub_date
2010-10-01 00:00:00pages
430-5issue
2eissn
0014-4886issn
1090-2430pii
S0014-4886(10)00259-1journal_volume
225pub_type
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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doi:10.1016/j.expneurol.2015.12.020
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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更新日期:1988-02-01 00:00:00
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journal_title:Experimental neurology
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更新日期:2015-01-01 00:00:00