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Int. J. Mol. Sci. 2019, 20(2), 304; https://doi.org/10.3390/ijms20020304

The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of Molecular Biology, Wita Stwosza 59, 80-308 Gdańsk, Poland
2
Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland
3
Department of Molecular Biology, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland
4
Laboratory of Electron Microscopy, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland
*
Author to whom correspondence should be addressed.
Received: 12 December 2018 / Revised: 3 January 2019 / Accepted: 7 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Molecular Features of Lysosomal Storage Disorders)
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Abstract

Obstacles to effective therapies for mucopolysaccharidoses (MPSs) determine the need for continuous studies in order to enhance therapeutic strategies. Dimethyl sulfoxide (DMSO) is frequently utilised as a solvent in biological studies, and as a vehicle for drug therapy and the in vivo administration of water-insoluble substances. In the light of the uncertainty on the mechanisms of DMSO impact on metabolism of glycosaminoglycans (GAGs) pathologically accumulated in MPSs, in this work, we made an attempt to investigate and resolve the question of the nature of GAG level modulation by DMSO, the isoflavone genistein solvent employed previously by our group in MPS treatment. In this work, we first found the cytotoxic effect of DMSO on human fibroblasts at concentrations above 3%. Also, our results displayed the potential role of DMSO in the regulation of biological processes at the transcriptional level, then demonstrated a moderate impact of the solvent on GAG synthesis. Interestingly, alterations of lysosomal ultrastructure upon DMSO treatment were visible. As there is growing evidence in the literature that DMSO can affect cellular pathways leading to numerous changes, it is important to expand our knowledge concerning this issue. View Full-Text
Keywords: lysosomal storage diseases; mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome); dimethyl sulfoxide (DMSO); glycosamoninoglycans (GAGs) therapy lysosomal storage diseases; mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome); dimethyl sulfoxide (DMSO); glycosamoninoglycans (GAGs) therapy
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Moskot, M.; Jakóbkiewicz-Banecka, J.; Kloska, A.; Piotrowska, E.; Narajczyk, M.; Gabig-Cimińska, M. The Role of Dimethyl Sulfoxide (DMSO) in Gene Expression Modulation and Glycosaminoglycan Metabolism in Lysosomal Storage Disorders on an Example of Mucopolysaccharidosis. Int. J. Mol. Sci. 2019, 20, 304.

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