Effect of glycosaminoglycans accumulation on the non-oxidative sulfur metabolism in mouse model of Sanfilippo syndrome, type B

Abstract

Lack of the N-alpha-acetylglucosaminidase gene is responsible for the occurrence of a rare disease – the Sanfilippo syndrome, type B. The result of this gene knock-out is accumulation of glycosaminoglycans (GAGs) – more specifically heparan sulfate – a sulfate rich macromolecule. The sulfur oxidative pathway is involved in the sulfate groups’ turnover in the cells. In contrast, the non-oxidative sulfur pathway leads mostly to formation of sulfane sulfur-containing compounds. The aim of our research was to observe an interaction between MPS IIIB and non-oxidative sulfur metabolism. In this work, we examined selected tissues (livers, kidneys, hearts and spleens) of 3 month old mice with confirmed accumulation of GAGs. The activity and expression of three sulfurtransferases (components of non-oxidative sulfur metabolism): rhodanese, 3-mercaptopyruvate sulfurtransferase and cystathionine γ-lyase was determined, as well as the sulfane sulfur level and the level of other low molecular sulfur-containing compounds (reduced and oxidized glutathione, cysteine and cystine). In all tested tissues, the sulfane sulfur and/or sulfurtransferases’ activities, as well as the cysteine content, underwent statistically significant changes. These correlations were also related to the sex of the tested animals. The obtained results indicated that accumulation of incompletely degraded GAGs in the tissues had affected the non-oxidative sulfur metabolism.

The Expression and Activity of Rhodanese, 3-Mercaptopyruvate Sulfurtransferase, Cystathionine γ-Lyase in the Most Frequently Chosen Cellular Research Models

“…0.5 nmole/mg protein ( Table 5 ). The highest value of cysteine level was observed in the Naglu −/− cells (2 nmole/mg protein), and this is likely a biochemical cellular response to the mutation existing in this line (the mutation likely causes an increase in the sulfate levels originating from undigested disaccharide—heparan sulfate) [ 36 , 40 ]. L-cysteine is also a direct substrate for GSH formation, and the results in Table 5 provide information about the glutathione level in the tested cell lines.…”

Hyaluronic Acid-Based Nanocapsules as Efficient Delivery Systems of Garlic Oil Active Components with Anticancer Activity

“…Both of them, together with formed allyl persulfide and reactive thiols such as GSH, in the system may undergo further metathesis and redox reaction to form a series of glutathione-and allyl-polysulfides (G-(S)n-A and A-(S)n-A, n = 2-6). When an excessive amount of GSH is available, these compounds could eventually be reduced by GSH to produce H 2 S. All of the enzymes we studied (CTH, MPST and TST) participate in a series of reactions leading to the generation of hydrogen sulfide [40,74]. Thus, it was reasonable to assume that in the capsDATS-treated group, the levels of sulfurtransferase activity and/or expression level of their genes would be altered that was expected.…”

Heparan Sulfate, Mucopolysaccharidosis IIIB and Sulfur Metabolism Disorders

“…On the cellular level, the disorder is characterized by the massive lysosomal storage of heparan sulfate (HS)-a sulfur-rich macromolecule. Accumulation of such molecules should affect the turnover of total sulfur in the cells, and, as Kaczor-Kami ńska and others showed [10,11], indeed, it does.…”