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

Moskot, Marta; Jakóbkiewicz‐Banecka, Joanna; Kłoska, Anna; Piotrowska, Ewa; Narajczyk, Magdalena; Gabig-Cimińska, Magdalena

doi:10.3390/ijms20020304

Cited by 32 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…15 Moskot et al studied the role of DMSO in gene modulation and glycosaminoglycan metabolism in lysosomal storage disorders. 16 Similarly, there is a distinct variation in expression patterns when hFLPCs were exposed to Rif and DMSO. We also show limited capacity of LA to induce differentiation in hFLPCs.…”

Section: Discussionmentioning

confidence: 99%

Xenobiotic-Induced Fetal Hepatocyte Maturation

Joshi

Gulbake

Kashte

et al. 2019

Applied In Vitro Toxicology

View full text Add to dashboard Cite

Introduction: Human fetal liver progenitor cells (hFLPCs) offer an emerging limitless source for generating mature hepatocytes that can be useful in cell therapies, as well as in pharmacological and toxicological studies. However, hFLPCs have very limited use over adult hepatocytes because of lower expression of drugmetabolizing enzymes. Here, we studied a novel method to achieve physiological maturity of fetal hepatocytes by exposing them to PXR and HNF4a agonist. Materials and Methods: We investigated the expression of cytochrome P450s (CYP3A4 and CYP2B10), glutathione S-transferase Mu 1 (GSTM1), UDP-glucuronosyltransferase 1-1 (UGT1A1), and drug transporters ATPbinding cassette subfamily C member (ABCC2 and ABCC3) by exposing them to rifampicin (Rif, 10 and 30 lM), linoleic acid (50 and 100 lM), and 0.1% dimethyl sulfoxide (DMSO) for 4, 8, and 12 days. The realtime polymerase chain reaction and western blotting were used to determine mRNA and protein expression of CYPs. Results: Increased CYP expression on the mRNA and protein level was detected in hFLPCs, which are exposed to DMSO-and Rif-treated cells that were much higher than in untreated. There was increase in levels of CYP2B10 protein with respect to time when hFLPCs exposed to DMSO. Discussion and Conclusions: Thus, this is the first report on expression of few phase I, II, and III enzymes in hFLPCs challenged with PXR and HNF4a agonists and to generate hFLPCs expressing drug-metabolizing enzymes similar to that of primary human adult hepatocytes.

show abstract

Section: Discussionmentioning

confidence: 99%

Xenobiotic-Induced Fetal Hepatocyte Maturation

Joshi

Gulbake

Kashte

et al. 2019

Applied In Vitro Toxicology

View full text Add to dashboard Cite

show abstract

“…DMSO at 0.1% v / v final concentration was used to solubilize the test compounds, except for compound 3b , 3c , and 3e , where 1% v / v DMSO was used to ensure complete solubilization. This concentration was based on our preliminary findings and reference [29] which suggested that exposure of human dermal fibroblast cultures for 48 h to concentrations reaching 1% v / v DMSO had no significant effect on cell viability.…”

Section: Methodsmentioning

confidence: 99%

Design and Synthesis of Matrine Derivatives as Novel Anti-Pulmonary Fibrotic Agents via Repression of the TGFβ/Smad Pathway

Wang

et al. 2019

Molecules

View full text Add to dashboard Cite

A total of 18 matrine derivatives were designed, synthesized, and evaluated for their inhibitory effect against TGF-β1-induced total collagen accumulation in human fetal lung fibroblast MRC-5 cell lines. Among them, compound 3f displayed the most potent anti-fibrotic activity (IC50 = 3.3 ± 0.3 μM) which was 266-fold more potent than matrine. 3f significantly inhibited the fibroblast-to-myofibroblast transition and extracellular matrix production of MRC-5 cells. The TGF-β/small mothers against decapentaplegic homologs (Smad) signaling was also inhibited by 3f, as evidenced by inhibition of cytoplasm-to-nuclear translocation of Smad2/3 and suppression of TGF-β1-induced upregulation of TGF-β receptor type I (TGFβRI). Additionally, 3f exhibited potent inhibitory effects against TGF-β1-induced fibroblasts migration. These data suggested that 3f might be a potential agent for the treatment of idiopathic pulmonary fibrosis via repression of the TGFβ/Smad signaling pathway.

show abstract

“…In vitro studies on normal (non-MPS) Chinese hamster ovary cells showed a large decrease in the synthesis of GAG (cell-bound and released to agar) under the influence of one of the organic compounds from the group of sulfoxides, dimethyl sulfoxide (DMSO) [ 52 ]. The experiments carried out many years later on fibroblasts from healthy donors and from patients with MPS IIIA and IIIB confirmed a moderate impact of DMSO on GAG synthesis [ 53 ]. Modulation of the expression of genes involved in GAG synthesis has been proposed as a mechanism for this phenomenon.…”

Section: Compounds With Antioxidant Activities and Their Effects In Mpsmentioning

confidence: 99%

Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications

et al. 2021

View full text Add to dashboard Cite

Although mucopolysaccharidoses (MPS) are caused by mutations in genes coding for enzymes responsible for degradation of glycosaminoglycans, storage of these compounds is crucial but is not the only pathomechanism of these severe, inherited metabolic diseases. Among various factors and processes influencing the course of MPS, oxidative stress appears to be a major one. Oxidative imbalance, occurring in MPS and resulting in increased levels of reactive oxidative species, causes damage of various biomolecules, leading to worsening of symptoms, especially in the central nervous system (but not restricted to this system). A few therapeutic options are available for some types of MPS, including enzyme replacement therapy and hematopoietic stem cell transplantation, however, none of them are fully effective in reducing all symptoms. A possibility that molecules with antioxidative activities might be useful accompanying drugs, administered together with other therapies, is discussed in light of the potential efficacy of MPS treatment.

show abstract

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

Cited by 32 publications

References 36 publications

Xenobiotic-Induced Fetal Hepatocyte Maturation

Xenobiotic-Induced Fetal Hepatocyte Maturation

Design and Synthesis of Matrine Derivatives as Novel Anti-Pulmonary Fibrotic Agents via Repression of the TGFβ/Smad Pathway

Oxidative Stress in Mucopolysaccharidoses: Pharmacological Implications

Contact Info

Product

Resources

About