title: Apparent cathepsin B deficiency in neuronal ceroid lipofuscinosis can be explained by peroxide inhibition.
abstract: Fibroblasts from patients with various forms of neuronal ceroid lipofuscinosis (NCL or Batten's disease) showed decreasing cathepsin B activity with increasing passage number and time in culture. In contrast, other lysosomal hydrolase activities were largely unaffected. Cathepsin B activity, was found to be associated with the lysosome-enriched fraction following cell disruption and Percoll gradient fractionation. Exposure of fibroblasts to low concentrations (less than 0.1 mM) of hydrogen peroxide either in vivo or in vitro resulted in a dose-dependent loss of cathepsin B activity with no concomitant loss in cathepsin H activity or lysosomal hydrolase activity. These results suggest that a primary defect resulting in accumulation of abnormal peroxides could produce a secondary cathepsin B inhibition in lysosomes and lead to observed peptide and dolichol accumulation in NCL.
mesh_terms: D002401:Cathepsin B / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology; D006596:Hexosaminidases / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000201:enzymology*
chemical_list: D008054:Lipid Peroxides; D006861:Hydrogen Peroxide; D006596:Hexosaminidases; D002401:Cathepsin B