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    Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production

    Access Status
    Fulltext not available
    Authors
    Carnagarin, R.
    Carlessi, R.
    Newsholme, P.
    Dharmarajan, Arunasalam
    Dass, C.
    Date
    2016
    Type
    Journal Article
    
    Metadata
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    Citation
    Carnagarin, R. and Carlessi, R. and Newsholme, P. and Dharmarajan, A. and Dass, C. 2016. Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production. International Journal of Biochemistry and Cell Biology. 78: pp. 229-236.
    Source Title
    International Journal of Biochemistry and Cell Biology
    DOI
    10.1016/j.biocel.2016.06.013
    ISSN
    1357-2725
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/38035
    Collection
    • Curtin Research Publications
    Abstract

    Pigment epithelium-derived factor is a multifunctional serpin implicated in insulin resistance in metabolic disorders. Recent evidence suggests that exposure of peripheral tissues such as skeletal muscle to PEDF has profound metabolic consequences with predisposition towards chronic conditions such as obesity, type 2 diabetes, metabolic syndrome and polycystic ovarian syndrome. Chronic inflammation shifts muscle metabolism towards increased glycolysis and decreased oxidative metabolism. In the present study, we demonstrate a novel effect of PEDF on cellular metabolism in mouse cell line (C2C12) and human primary skeletal muscle cells. PEDF addition to skeletal muscle cells induced enhanced phospholipase A2 activity. This was accompanied with increased production of reactive oxygen species in a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent manner that triggered a shift towards a more glycolytic phenotype. Extracellular flux analysis and glucose consumption assays demonstrated that PEDF treatment resulted in enhanced glycolysis but did not change mitochondrial respiration. Our results demonstrate that skeletal muscle cells express a PEDF-inducible oxidant generating system that enhances glycolysis but is sensitive to antioxidants and NADPH oxidase inhibition.

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