title: Biotin-dependent carboxylase activities in different CNS and skin-derived cells, and their sensitivity to biotin-depletion.
abstract: The validity of various transformed and untransformed CNS and skin-derived cell cultures as a model for studying effects of biotin deficiency was tested. In biotin-sufficient conditions (0.1-10 mumol/L) all cell types showed considerable activities of the four biotin-dependent carboxylases. Notably, pyruvate carboxylase activity was also present in the different neuronal cells. One passage in low-biotin medium (6-130 pmol/L) lowered mitochondrial carboxylase activities in all cell types, but to varying degrees. Sensitivity to biotin depletion was greatest in three neuronal cell types, Roc-1 oligodendroglia, and three keratinocyte cell types (carboxylase activities decreased to 2-11% of maximal); intermediate in primary astrocytes and C6 glioma (decreased to 12-28%), and least in SAOS2 sarcoma and skin fibroblasts (decreased to 32-85%). Transformed and untransformed cell lines of the same cell type showed similar sensitivity. We conclude that cultures of different transformed CNS and keratinocyte cell types allow the study of effects of biotin deprivation. Carboxylase activities of neurons, oligodendroglia, and keratinocytes were much more sensitive to biotin depletion than fibroblasts. This may be an important factor in the pathogenesis of neurological and cutaneous abnormalities in congenital biotinidase deficiency where recycling of biotin is deficient.
authors.affiliation: Metabolic Unit, University Children's Hospital, Römergasse 8, CH-4005 Basel, Switzerland. Terttu.Suormala@unibas.ch
authors.forename: Terttu
authors.initials: T
authors.lastname: Suormala
authors.forename: Ulrich N
authors.initials: UN
authors.lastname: Wiesmann
authors.forename: Fatima
authors.initials: F
authors.lastname: Cruz
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Markus
authors.initials: M
authors.lastname: Daschner
authors.forename: Alain
authors.initials: A
authors.lastname: Limat
authors.forename: Brian
authors.initials: B
authors.lastname: Fowler
authors.forename: E Regula
authors.initials: ER
authors.lastname: Baumgartner
mesh_terms: D000818:Animals; D001710:Biotin / Q000172:deficiency* / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003470:Culture Media; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D009836:Oligodendroglia / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism
chemical_list: D003470:Culture Media; D001710:Biotin; D002262:Carboxy-Lyases