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)

Cultures of cells dissociated from embryonic mouse brain were used to assess the period in which thyroid hormone exerts its maximum influence on the regulation of the expression of two myelin associated metabolites, sulfolipids and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP-ase). Cultures were grown for a specified number of days on a medium containing normal calf serum and then a portion were switched to a medium containing hypothyroid calf serum for 2 days. One half of these cultures were then supplemented with 50 nM triiodothyronine and growth was continued in all cultures for 3 more days. The cells were then assayed for CNP-ase activity and for their ability to incorporate 35SO4 into sulfolipids. Studies with both myelin markers showed that in the earlier culture ages of 5, 8, and 11 days, thyroid hormone was able to fully restore the activities when added to cultures grown on hypothyroid calf-serum. In contrast, in the intermediate age range (15, 19, and 22 days) the restoration was partial, while in the higher ages, there was practically negligible restoration with T3. Since the culture system eliminates the possibility of a blood brain barrier and drastically decreases the complicity of other hormones, the lack of a myelinogenic response to thyroid hormone after a certain age must be attributed to the loss of sensitivity of the oligodendroglia to T3 possibly through genetic programming.
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PMID:Investigations on myelinogenesis in vitro: a study of the critical period at which thyroid hormone exerts its maximum regulatory effect on the developmental expression of two myelin associated markers in cultured brain cells from embryonic mice. 298 18

Hypothyroidism was induced in rats by treatment with propylthiouracil through the mother's milk throughout the suckling period followed by surgical thyroidectomy without use of radioiodine. The growth of these animals was considerably retarded and their light-dark discriminative operant learning ability was also significantly decreased. Replacement therapy with thyroxine to maintain its normal serum concentration was effective for continuing normal growth and development of learning ability. Therefore, these hypothyroid rats are a useful model of congenital hypothyroidism. Biochemical studies showed that the inhibition of cerebral Na,K-ATPase and succinic dehydrogenase activities detected in early postnatal life in these hypothyroid rats was transient and that normal activities of these enzymes were later regained in adult rats. However, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase and the brain myelin remained low throughout life unless thyroxine was administered. Though a critical correlation between biochemical parameters and learning ability is still uncertain, these results suggest that the formation of myelin in the neonatal period is at least dependent on thyroid hormone and would play an important role in mental development.
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PMID:An appropriate model for congenital hypothyroidism in the rat induced by neonatal treatment with propylthiouracil and surgical thyroidectomy: studies on learning ability and biochemical parameters. 339 29

We attempted to define whether thyroid hormone can ameliorate the cerebral hypomyelination present in the congenitally hypothyroid (hyt) neonatal mouse, and to define the critical time period during early postnatal life when thyroxine (T4) is essential for myelin formation. We administered T4 to the hyt mouse by breast milk during the first 20 days of postnatal life, and through the diet during the second 20 days of postnatal life. Positive results were obtained only when hormone was given during the first 20 days of postnatal life. A distinct increase in cerebral 2',3'-cyclic nucleotide 3'-phosphohydrolase activity was noted, and brain sections stained for myelin basic protein correlated with the biochemical findings. The later administration of hormone through diet was ineffective.
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PMID:Partial restoration of cerebral myelination of the congenitally hypothyroid mouse by parenteral or breast milk administration of thyroxine. 404 55

L-3,5,3'-Triiodothyronine (T3) has been shown to influence the synthesis of myelin-associated lipids in cultures of cells dissociated from brains of embryonic mice (Bhat, N. R., Sarlieve, L., Subba Rao, G., and Pieringer, R. A. (1979) J. Biol. Chem. 254, 9342-9344). This culture system was used in the present study to gain additional information on the regulation of the synthesis of myelin lipids by thyroid hormone. The rate of synthesis of the myelin associated sulfolipids remained drastically diminished throughout a 70-day developmental period when cells were grown in the presence of hypothyroid calf serum (T3 < 25 ng/100 ml; thyroxine (T4), 1.2 microgram/ml). However, the activity could be restored to normal levels after 72 h of exposure to deficient medium supplemented with exogenous T3. Half-maximal effects were obtained with 2 X 10(-9) M T3 and 6.25 X 10(-7) M T4. T3 does not alter the synthesis of sulfated mucopolysaccharides, which share adenosine 3'-phosphate, 5'-phosphosulfate (PAPS), as a common precursor, with sulfolipids. This observation argues against the hormone altering the entry of sulfate or the synthesis of PAPS. Rather, T3 acts by changing the activity of the glycolipid:PAPS sulfotransferase(s) in direct proportion to the concentration of T3 in the growth medium. The activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, another myelin marker was also found to be T3 dependent. The response of sulfolipid synthesis to varying amounts of T3 was also observed in a serum-free medium, which suggests that T3 can function independently of other hormones and serum factors in exerting a relatively specific effect on the regulation of myelination.
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PMID:Investigations on myelination in vitro. Regulation of sulfolipid synthesis by thyroid hormone in cultures of dissociated brain cells from embryonic mice. 625 88

To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.
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PMID:Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development. 910 69

The effects of hypothyroidism on oligodendroglial differentiation and myelination are for the first time studied by immunohistochemical localization of an early oligodendroglial marker, the 2'3'cyclic nucleotide 3'phosphodiesterase (E.C. 3.1.4.37-CNPase), in developing rats. Two groups received methimazol; one during gestation (H) and another postnatally (PN). One H sub-group received thyroxine after birth (T). We observed a delay in CNPase expression followed by a decrease in the number of CNPase immunoreactive fibers in both H and PN groups. The T sub-group was not different from controls. Furthermore, the immunoreactive fibers, in mature hypothyroid animals, showed a continuous pattern of staining in contrast with a discontinuous one in controls. Myelinogenesis is a highly regulated timed event. CNPase links myelin related proteins to the cytoskeleton also interacting with membrane lipids during extension and wrapping of the oligodendroglial process around the axon (ensheathment phase). In mature myelinated fiber the CNPase is absent from compact myelin sheath, being located only in the inner and outer loops and in paranodal loops. Thus, our data suggest a disorder in myelin compaction and point once more to the post-natal period as critical for the mechanisms that are thyroid hormone regulated in myelinogenesis.
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PMID:2'3'Cyclic nucleotide 3'phosphodiesterase immunohistochemistry shows an impairment on myelin compaction in hypothyroid rats. 1115 57

Terminal differentiation of oligodendrocytes is associated with permanent withdrawal from the cell cycle. We studied the expression of the retinoblastoma protein, expression and activity of G1 cyclins and kinases in oligodendrocyte progenitor cells cultured in vitro. We found that Rb stopped to be expressed concomitantly with the activation of CNPase in oligodendrocytes differentiated with thyroid hormone. In contrast, Rb continued to be expressed at reduced levels in oligodendrocytes that were arrested in G1 by removal of mitogens. Cyclin D1, cdk2, and cdk4 kinase activities were decreased in G1-arrested and differentiated oligodendrocytes. Cyclin E, however, continued to be expressed in G1-arrested oligodendrocytes. Inhibition of differentiation induced by mitogens in oligodendrocytes arrested in G1 by Ad-p27 was accompanied by continued expression of Rb, D1, and E cyclins. After removal of mitogens and addition of thyroid hormone, Rb stopped being expressed and CNPase expression was activated with a temporal course similar to that of oligodendrocytes infected with a control adenovirus. Our results indicate that Rb may play an important function in differentiation of oligodendrocytes in response to external mitogens and differentiation factors.
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PMID:Down-regulation of the retinoblastoma protein (rb) is associated with rat oligodendrocyte differentiation. 1186 Feb 77

The cellular responses to a brain injury are important steps in restoring the integrity and function of the brain. Proliferating cells, such as reactive astrocytes, oligodendrocyte precursor cells and microglia remodel the injured tissue. To spatially and temporally characterize the initial cellular responses in vivo, proliferating cells were pulse-labeled with BrdU soon after (the 2nd day) a cortical cryo-injury, and their fate was investigated by double labeling with an anti-BrdU antibody and antibodies to various cellular markers. Three days after the cryo-injury, a significant proportion of BrdU-positive cells were positive for NG2-proteoglycan, suggesting that oligodendrocyte progenitors (OPCs) were induced in response to injury. One-two weeks after the cryo-injury, the number of OPC was reduced and GFAP/BrdU double-positive cells, in turn, became dominant, while cells with mature oligodendrocyte markers did not increase significantly. Neuronal markers were rarely co-localized with BrdU immunoreactivity throughout the period studied. These findings imply that OPCs are prone to differentiate to astrocytes in the lesioned site. In this cryo-injury model, treatment with thyroid hormone (T4) altered cell fate; the increase in the number of GFAP/BrdU-positive cells was significantly diminished, and there was an increased number of mature oligodendrocytes (CNPase, PLP-positive) exhibiting BrdU immunoreactivity. These findings suggest that modification of proliferating progenitors in injured brain by hormonal or chemical treatment might benefit functional regeneration.
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PMID:Characterization of cells with proliferative activity after a brain injury. 1573 36

Polychlorinated dibenzo-dioxins, furans and dioxin-like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a lipophilic endocrine-disrupting molecule that accumulates in adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known to interfere with thyroid hormone metabolism and signaling in the developing brain. As thyroid hormone is critical in the myelination process during development, we investigated the effect of a single dose of TCDD prenatal exposure (gestational day 18) on the myelination process. A semi-quantitative analysis of oligodendrocyte markers at different stages of maturation was performed in the offspring's medulla oblongata, cerebellum, diencephalon and telenchephalon at different postnatal days (2/3, 14, 30 and 135). The most significant alterations observed were: (i) cerebellum and medulla oblongata: altered expression of oligodendroglial lineage and platelet-derived growth factor alpha receptor, myelin basic protein (MBP) mRNAs (P2/3, P135) and MBP protein (P135); (ii) diencephalon: increase in platelet- derived growth factor alpha receptor mRNA level (P2/3); (iii) telenchephalon: decrease in MBP mRNA expression. The oligodendroglial generation capability of adult neural stem/precursor cells obtained ex vivo from TCDD and vehicle-treated dams was then explored. TCDD impairs neurosphere proliferation and retards CNPase-positive cell generation from adult neurospheres.
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PMID:A single prenatal exposure to the endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin alters developmental myelination and remyelination potential in the rat brain. 2080 17