title: Psychosine-induced alterations in peroxisomes of twitcher mouse liver.
abstract: Krabbe disease is a neuroinflammatory disorder in which galactosylsphingosine (psychosine) accumulates in nervous tissue. To gain insight into whether the psychosine-induced effects in nervous tissue extend to peripheral organs, we investigated the expression of cytokines and their effects on peroxisomal structure/functions in twitcher mouse liver (animal model of Krabbe disease). Immunofluorescence analysis demonstrated TNF-alpha and IL-6 expression, which was confirmed by mRNAs quantitation. Despite the presence of TNF-alpha, lipidomic analysis did not indicate a significant decrease in sphingomyelin or an increase in ceramide fractions. Ultrastructural analysis of catalase-dependent staining of liver sections showed reduced reactivity without significant changes in peroxisomal contents. This observation was confirmed by assaying catalase activity and quantitation of its mRNA, both of which were found significantly decreased in twitcher mouse liver. Western blot analysis demonstrated a generalized reduction of peroxisomal matrix and membrane proteins. These observations indicate that twitcher mouse pathobiology extends to the liver, where psychosine-induced TNF-alpha and IL-6 compromise peroxisomal structure and functions.
authors.affiliation: Department of Pediatrics and The Charles Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Miguel Agustin
authors.initials: MA
authors.lastname: Contreras
authors.forename: Ehtishamul
authors.initials: E
authors.lastname: Haq
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.forename: Inderjit
authors.initials: I
authors.lastname: Singh
authors.forename: Avtar Kaur
authors.initials: AK
authors.lastname: Singh
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism*; D011609:Psychosine / Q000008:administration & dosage*; D014018:Tissue Distribution
chemical_list: D016207:Cytokines; D011609:Psychosine