title: TNF-α upregulates macroautophagic processing of APP/β-amyloid in a human rhabdomyosarcoma cell line.
abstract: Sporadic inclusion body myositis is a chronic progressive, inflammatory disorder of the skeletal muscle. No effective treatment is available for this debilitating condition and the complex disease pathology is far from being understood. The major hallmark of the pathomechanisms is the co-occurrence of inflammatory as well as degenerative cascades including aggregates consisting of β-amyloid within skeletal muscle fibers. Macroautophagy, a homeostatic process that shuttles cytoplasmic constituents into endosomal and lysosomal compartments, has recently been shown to be upregulated via the proinflammatory cytokine TNF-α in human skeletal muscle cells. In a human cell line from rhabdomyosarcoma as a model to study muscle cells, we here show that TNF-α-mediated upregulation of macroautophagy modulates APP and β-amyloid load and can be blocked by inhibition of macroautophagy. Thus, macroautophagy may be a crucial mediator between inflammation and β-amyloid-associated degeneration in skeletal muscle.
authors.affiliation: Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Keller
authors.forename: Matthias
authors.initials: M
authors.lastname: Schmitz
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.forename: Jan D
authors.initials: JD
authors.lastname: Lünemann
authors.forename: Jens
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D009220:Myositis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C078592:amyloid beta-protein (1-40)