Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of low (physiological) concentrations of insulin (2 and 20 ng/ml) and L-triiodothyronine (T3) were studied on two myelin-related enzymes: (1) the 3'-phosphoadenosine-5'-phosphosulfate:cerebroside sulfotransferase (CST, EC 2.8.2.11) catalyzing the production of sulfatide, and (2) the myelin enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP, EC 3.1.4.3.7) in myelinogenic cultures of cells dissociated from embryonic mouse brain. Insulin treatment (20 ng/ml) of the cells in the presence of serum increased CST activity at 18 and 25 days in vitro (DIV) by 86 and 211%, respectively. At 18 DIV and under the same conditions, CNP was significantly stimulated (95%) by high doses of insulin (2,000 ng/ml) only, while arylsulfatase A (EC 3.1.6.1) or cerebroside sulfatase activities, both of which are involved in sulfatide degradation, were unchanged. Thus, it can be assumed that the observed increase of the incorporation of [35S]O4 into sulfatide after insulin treatment of mixed cell cultures is the result of CST induction rather than a decreased catabolism. The level of CST activity in insulin-treated cells (20 ng/ml) in serum-free medium was also increased at 18 and 25 DIV by about 50 and 70%, respectively. Conversely, none of the insulin concentrations used in the absence of serum (even at high doses) had any effect, either at 18 or 25 DIV on CNP and ASA activities. The involvement of insulin in the regulation of sulfatide synthesis was further confirmed by dose-response curves relating the activity of CST to hormone concentration in the medium. The increase in the activity of CST in insulin-treated cells was due only to the increase in the Vmax of this enzyme, suggesting that it may be attributed to enzyme induction. A study of kinetic parameters of CST indicated that there were no differences in pH optimum and Km values between control and induced enzyme. Further experiments using cycloheximide point to a direct effect of insulin on oligodendrocyte CST induction. Data similar to those described above for insulin were also obtained with T3. As for insulin, T3 stimulated the induction of CST but in serum-free medium only. This effect was prevented by cycloheximide. In addition, the induction of CST by T3 was blocked by actinomycin D. This was not the case for insulin. These results suggest that T3 and insulin act on CST by different mechanisms, i.e. at transcriptional and post-translational levels, respectively. Apart from this, the insulin effect on CST activity was additive to that of T3.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Comparison of the mechanisms of action of insulin and triiodothyronine on the synthesis of cerebroside sulfotransferase in cultures of cells dissociated from brains of embryonic mice. 218 27

Net sulfatide synthesis, galactosylceramide sulfotransferase (EC 2.8.2.11) and arylsulfatase A (EC 3.1.6.1) activities were measured in two brain regions, cerebrum and cerebellum, of normal and jimpy mice during postnatal development. In normally myelinating mice, two phases of increasing rates of net sulfatide synthesis were observed, the first coinciding with oligodendrocyte proliferation and the second with myelination. Net sulfatide synthesis was quantitatively higher in the cerebellum than in the cerebrum. In both brain regions, the developmental patterns of net sulfatide synthesis were related to the activity patterns of both galactosylceramide sulfotransferase and arylsulfatase A. In jimpy mice, a neurological mutant showing hypomyelination in brain, the first phase of net sulfatide synthesis was preserved in both brain regions and galactosylceramide sulfotransferase and arylsulfatase A activities were normal up to 12 days. However, during the phase in which myelination occurred in controls, the net sulfatide synthesis in both brain regions of jimpy mice was zero or even negative. The sulfatide deficit was larger in the cerebellum than in the cerebrum. In both mutant brain parts, galactosylceramide sulfotransferase activity increased up to 12 days showing about 50% of the maximal activities observed in normal brain regions. Thereafter up to 15 days, enzyme activity decreased to about 25% of that of controls and remained low in both brain regions. The developmental patterns and the activities of arylsulfatase A were, however, normal in the cerebrum and cerebellum of jimpy mice. These results suggest that the enzyme activities and the developmental patterns of galactosylceramide sulfotransferase and arylsulfatase A as measured in vitro reflect to a high degree their functional activity in vivo. Furthermore, sulfatide degradation by arylsulfatase A seems to be important in regulating net sulfatide synthesis during normal and impaired myelination.
 ...
PMID:Net sulfatide synthesis, galactosylceramide sulfotransferase and arylsulfatase A activity in the developing cerebrum and cerebellum of normal mice and myelin-deficient jimpy mice. 611 19

Accumulation of sulfolipids associated with markedly elevated levels of glycolipid sulfotransferase activities was previously demonstrated in human renal cell carcinoma cells. To explore the regulation mechanisms of sulfoglycolipid synthesis in renal cancer, effects of various growth factors on the metabolic enzymes of sulfoglycolipids were investigated by using a human renal cell carcinoma cell line, SMKT-R3. Among the growth factors tested, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to increase the sulfotransferase activity markedly (about 300%), but did not change that of arylsulfatase A, which hydrolyzes sulfoglycolipids. The augmented effects of TGF-alpha was abolished by cycloheximide. Since TGF-alpha is known to bind to the same receptor as EGF, SMKT-R3 cells were investigated for the EGF receptor by affinity cross-linking with 125I-EGF. A radiolabeled protein with a molecular mass of 175 kDa corresponding to the ligand-receptor complex was immunoprecipitated with a monoclonal anti-EGF receptor antibody. When production of the growth factors was examined immunochemically, the cells were found to secrete TGF-alpha at a low level and retain it in a membrane-bound form, whereas EGF was not detected. These observations suggest that the sulfotransferase activities are regulated through the autocrine, paracrine, and/or juxtacrine modes of intercellular stimulation by TGF-alpha in human renal cancer cells.
 ...
PMID:Regulation of activity levels of glycolipid sulfotransferases by transforming growth factor alpha in renal cell carcinoma cells. 790 7

Lead is a neurotoxicant that can cause myelin deficits. Galactolipids are expressed during differentiation of oligodendrocyte lineage cells and accumulate in myelin. To examine the impact of lead on oligodendroglial differentiation, galactolipid metabolism in cultured oligodendrocyte lineage cells exposed to the metal was studied. Oligodendrocyte progenitor cells obtained from newborn rat pups were exposed to 1 microM lead acetate for 24 h prior to maintenance of the cells in medium containing the metal salt for 0, 2, or 6 days of differentiation. Lead caused approximately 50% reduction in levels of the galactolipid biosynthetic transferases, UDP-galactose:ceramide galactosyltransferase and 3'-phosphoadenosine-5'-phosphosulfate:galactocerebroside sulfotransferase, as compared to sodium-treated controls, in cultures of oligodendrocyte lineage cells following 2 days of differentiation. The activities of the galactolipid catabolic hydrolases, galactocerebroside-beta-galactosidase and arylsulfatase A, were reduced by 20%. Following 6 days of differentiation, lead-exposed cells exhibited levels of all the enzymes, except for arylsulfatase A, similar to those of the control cells. These results are consistent with the lead-induced delay of oligodendrocyte differentiation, as evidenced by the emergence of stage-specific immunochemical markers and the observed change in the developmental activity profile of 2',3'-cyclic nucleotide 3'-phosphohydrolase. The activity of arylsulfatase A in lead-treated 6-day oligodendrocytes was significantly less than that found in control cultures. This effect is consistent with the lead-induced reduction of arylsulfatase A in human fibroblasts caused by mis-sorting the newly-synthesized enzyme. The perturbation of galactolipid metabolism by lead during developmental maturation of oligodendrocytes may represent a contributing mechanism for lead-induced neurotoxicity.
 ...
PMID:Lead alters the developmental profile of the galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells. 1157 1