Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.37 (CNPase)
 539 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)
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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

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.
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PMID:Lead alters the developmental profile of the galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells. 1157 1

Brain composition and developmental changes were investigated in mice homozygous for the locus "dwarf," and characterized by a reduced level of growth hormone, thyroid stimulating hormone, and prolactin, and by secondary hypothyroidism. The difference in adult brain weight (-32%) between the dwarf and the normal mice was not found to parallel the difference in body weight (-71%), whereas the differences in the weight of the liver (-79%) and that of the kidney (-75%) did. Several biochemical parameters of brain development were assayed in dwarf and normal mice between the ages of 15 and 210 days. Levels of cerebrosides, sulfatides, gangliosides, phospholipids, cholesterol, protein, and RNA (per gram wet weight) were the same for the dwarf and the controls, but the net difference in total brain DNA was less than the net total brain RNA difference (-11% vs. -27%). Total brain lipids (absolute quantities) were the same at 15 days. The difference was -37% by the 50th day, and remained constant thereafter. No change in the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase or 3'-phosphoadenosine-5'-phosphosulfate: galactocerebroside sulfotransferase was observed. These data suggest that the regulation of the development of brain structures is maintained, but the level of the synthesis of the various brain constituents is reduced in proportion to the brain weight. The development of the dwarf brain seems to proceed harmoniously.
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PMID:Changes in brain components during the development of mice homozygous for the locus "dwarf" (dw)(1,5.). 2427 46