title: Activities of genes controlling sphingolipid metabolism in human fibroblasts treated with flavonoids.
abstract: Natural flavonoids such as genistein, kaempferol and daidzein were previously found to be able to reduce efficiency of glycosaminoglycan synthesis in cells of patients suffering from mucopolysaccharidoses, inherited metabolic diseases with often brain disease symptoms. This feature was employed to test these compounds as potential drugs for treatment other neuronopathic lysosomal storage disorders, in which errors in sphingolipid metabolism occur. In this report, on the basis of DNA microarray analyses and quantitative real time PCR experiments, we present evidence that these compounds modify expression of genes coding for enzymes required for metabolism of sphingolipids in human dermal fibroblasts (HDFa). Expression of several genes involved in sphingolipid synthesis was impaired by tested flavonoids. Therefore, it is tempting to speculate that they may be considered as potential drugs in treatment of LSD, in which accumulation of sphingolipids, especially glycosphingolipids, occurs. Nevertheless, further studies on more advances models are required to test this hypothesis and to assess a therapeutic potential for flavonoids in this group of metabolic brain diseases.
authors.affiliation: Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Moskot
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.forename: Elwira
authors.initials: E
authors.lastname: Smolińska
authors.forename: Bogdan
authors.initials: B
authors.lastname: Banecki
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gabig-Cimińska
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013107:Sphingolipids / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D013107:Sphingolipids