The role of dimethyl sulfoxide (DMSO) in gene expression modulation and glycosaminoglycan metabolism in lysosomal storage disorders on an example of mucopolysaccharidosis

Marta Moskot , Joanna Jakóbkiewicz-Banecka , Anna Kloska , Ewa Piotrowska , Magdalena Narajczyk , Magdalena Gabig-Cimińska

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.
Author Marta Moskot (FB / DMBG)
Marta Moskot,,
- Katedra Biologii i Genetyki Medycznej
, Joanna Jakóbkiewicz-Banecka (FB / DMBG)
Joanna Jakóbkiewicz-Banecka,,
- Katedra Biologii i Genetyki Medycznej
, Anna Kloska (FB / DMBG)
Anna Kloska,,
- Katedra Biologii i Genetyki Medycznej
, Ewa Piotrowska (FB / DMoB)
Ewa Piotrowska,,
- Department of Molecular Biology
, Magdalena Narajczyk (FB / LEM)
Magdalena Narajczyk,,
- Laboratory of Electron Microscopy
, Magdalena Gabig-Cimińska (FB / DMBG) - [Polish Academy of Science]
Magdalena Gabig-Cimińska,,
- Katedra Biologii i Genetyki Medycznej
- Polska Akademia Nauk
Journal seriesInternational Journal of Molecular Sciences, ISSN 1422-0067, (A 30 pkt)
Issue year2019
Vol20
No2
Pages1-18
Keywords in Englishlysosomal storage diseases, mucopolysaccharidosis type III (MPS III; Sanfilippo syndrome), dimethyl sulfoxide (DMSO), glycosamoninoglycans (GAGs) therapy
ASJC Classification1604 Inorganic Chemistry; 1605 Organic Chemistry; 1606 Physical and Theoretical Chemistry; 1706 Computer Science Applications; 1607 Spectroscopy; 1312 Molecular Biology; 2700 General Medicine; 1503 Catalysis
DOIDOI:10.3390/ijms20020304
URL https://doi.org/10.3390/ijms20020304
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)30
ScoreMinisterial score = 30.0, 14-03-2019, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 14-03-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 1.147; WoS Impact Factor: 2017 = 3.687 (2) - 2017=3.878 (5)
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