Calcineurin activates NF-kappaB in skeletal muscle C2C12 cells.
Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappaB activation by CnA was associated with elevated phospho-IkappaBalpha, and could be repressed by specific genetic (porZAKI-4 and porDSCR1) and chemical (cyclosporin A) inhibitors of CnA, but tumour necrosis factor-alpha (TNF-alpha) appeared not to be a key component in the cross-talk. Functionally, CnA-induced NF-kappaB activation seemed to interfere with terminal muscle differentiation. We therefore showed a functional interaction between the CnA and NF-kappaB pathways in skeletal muscle cells, which involved opposing phenotypic effects of CnA.
Alzuherri
Hadi
H
Veterinary Molecular Medicine Laboratory, Department of Veterinary Pathology, University of Glasgow, Bearsden Road, Glasgow G61 1QH, Scotland, UK.
Chang
Kin Chow
KC
D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019703:Calcineurin