Autophagosome-like vacuole formation in Huntington's disease lymphoblasts.
In an effort to clarify cellular abnormalities in Huntington's disease without the confounding factor of gross degeneration and postmortem alterations associated with studies of the brain, we have examined HD patient lymphoblasts. We report pronounced vacuole formation in patients. The vacuoles possess huntingtin remnants and cathepsin B staining, a lysosomal marker, suggesting autophagy. The number and size of vacuoles parallel the number of polyglutamine repeats in patients. Treatment with staurosporine, which augments apoptosis, leads to increased vacuole formation in Huntington's disease cells but does not influence control cells. Our findings provide direct evidence for abnormalities in Huntington's disease tissues outside the brain under basal conditions. Autophagic cellular alterations may be utilized as peripheral markers of Huntington's disease pathology.
Nagata
Eiichiro
E
Departments of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
Sawa
Akira
A
Ross
Christopher A
CA
Snyder
Solomon H
SH
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers; D002401:Cathepsin B / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D019311:Staurosporine / Q000494:pharmacology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014617:Vacuoles / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D015415:Biomarkers; D004791:Enzyme Inhibitors; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D002401:Cathepsin B; D019311:Staurosporine