Cell cycle is disturbed in mucopolysaccharidosis type II fibroblasts, and can be improved by genistein
| Autor: | Marta Moskot, Magdalena Gabig-Cimińska, Katarzyna Bocheńska, Grzegorz Węgrzyn, Joanna Jakóbkiewicz-Banecka, Magdalena Węsierska |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Cell division Mucopolysaccharidosis I Genistein Biology Cell Line Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics Humans MTT assay Mucopolysaccharidosis type II skin and connective tissue diseases Cell Proliferation Glycosaminoglycans Mucopolysaccharidosis II Cell growth Cell Cycle nutritional and metabolic diseases General Medicine Fibroblasts Cell cycle Molecular biology 030104 developmental biology chemistry Biochemistry Cell culture Cell Division 030217 neurology & neurosurgery |
| Zdroj: | Gene. 585:100-103 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2016.03.029 |
| Popis: | Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by mutations resulting in deficiency of one of enzymes involved in degradation of glycosaminoglycans (GAGs). These compounds accumulate in cells causing their dysfunctions. Genistein is a molecule previously found to both modify GAG metabolism and modulate cell cycle. Therefore, we investigated whether the cell cycle is affected in MPS cells and if genistein can influence this process. Fibroblasts derived from patients suffering from MPS types I, II, IIIA and IIIB, as well as normal human fibroblasts (the HDFa cell line) were investigated. MTT assay was used for determination of cell proliferation, and the cell cycle was analyzed by using the MUSE® Cell Analyzer. While effects of genistein on cell proliferation were similar in both normal and MPS fibroblasts, fractions of cells in the G0/G1 phase were higher, and number of cells entering the S and G2/M phases was considerably lower in MPS II fibroblasts relative to control cells. Somewhat similar tendency, though significantly less pronounced, could be noted in MPS I, but only at longer times of incubation. However, this was not observed in MPS IIIA and MPS IIIB fibroblasts. Genistein (5, 7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) was found to be able to partially correct the disturbances in the MPS II cell cycle, and to some extent in MPS I, at higher concentrations of this compound. The tendency to increase the fractions of cells entering the S and G2/M phases was also observed in MPS IIIA and IIIB fibroblasts treated with genistein. In conclusion, this is the first report indicating that the cell cycle can be impaired in MPS cells. The finding that genistein can improve the MPS II (and to some extent also MPS I) cell cycle provides an input to our knowledge on the molecular mechanisms of action of this compound. |
| Databáze: | OpenAIRE |
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