Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.3 (ascorbate oxidase)
 778 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ascorbate (0-500 microM) stimulates synthesis and secretion of collagen by cartilage explants in a dose-dependent fashion as estimated by [3H]proline incorporation. Concurrent elaboration of inorganic pyrophosphate (PPi) parallels [3H]proline incorporation (less than 0.001, Wilcoxon rank sum). The effect on proline and PPi is abolished by ascorbate oxidase. Another reducing agent, Vitamin E, did not promote PPi accumulation about cartilage. Inhibitors of collagen synthesis, including monensin, tumor necrosis factor alpha, and 2',2'dipyridyl also inhibited PPi elaboration. Cycloheximide (1 micrograms/ml) inhibited the ascorbate stimulated PPi elaboration 54% but did not attenuate the secretion of PPi by unstimulated cartilage. Cosecretion of collagen and PPi by chondrocytes may explain these results. Moreover, at least two pathways exist for PPi elaboration, a cycloheximide sensitive path and another independent of new protein synthesis.
 ...
PMID:Stimulation of cartilage inorganic pyrophosphate elaboration by ascorbate. 165 74

Embryonic neuronal tissues contain a collagen-stimulating factor, shown to enhance the hydroxylation and secretion of proline-containing macromolecules by cultured muscle cells. Here we report on a similar activity found during avian embryonic development in explants of migrating mesencephalic neural crest. The degree of proline hydroxylation of proteins secreted into the medium was stimulated 2.5-6-fold in neural crest-muscle and neural crest-somite cocultures, as compared with control cultures devoid of crest explants. No such stimulation occurred when cocultures were treated with the enzyme ascorbate oxidase (EC 1.10.3.3), suggesting that the active factor in neural crest explants was ascorbic acid or an ascorbate-like molecule. Further characterization of this molecule was performed in crest explants and other embryonic tissues by using HPLC with amperometric detection: this study revealed that migrating cephalic neural crest contains 1.5 micrograms ascorbic acid per mg protein. Our results suggest that ascorbic acid and/or related molecule(s) could act during development of the nervous system as a trigger for collagen production and subsequent assembly of an extracellular matrix.
 ...
PMID:Stimulation of collagen production in vitro by ascorbic acid released from explants of migrating avian neural crest. 283 31

Rat Schwann cells cultured with dorsal root ganglion neurons in a serum-free defined medium fail to ensheathe or myelinate axons or assemble basal laminae. Replacement of defined medium with medium that contains human placental serum (HPS) and chick embryo extract (EE) results in both basal lamina and myelin formation. In the present study, the individual effects of HPS and EE on basal lamina assembly and on myelin formation by Schwann cells cultured with neurons have been examined. Some batches of HPS were unable to promote myelin formation in the absence of EE, as assessed by quantitative evaluation of cultures stained with Sudan black; such HPS also failed to promote basal lamina assembly, as assessed by immunofluorescence using antibodies against laminin, type IV collagen, and heparan sulfate proteoglycan. The addition of EE or L-ascorbic acid with such HPS led to the formation of large quantities of myelin and to the assembly of basal laminae. Pretreatment of EE with ascorbic acid oxidase abolished the EE activity, whereas trypsin did not. Other batches of HPS were found to promote both basal lamina and myelin formation in the absence of either EE or ascorbic acid. Ascorbic acid oxidase treatment or dialysis of these batches of HPS abolished their ability to promote Schwann cell differentiation, whereas the subsequent addition of ascorbic acid restored that ability. Ascorbic acid in the absence of serum was relatively ineffective in promoting either basal lamina or myelin formation. Fetal bovine serum was as effective as HPS in allowing ascorbic acid (and several analogs but not other reducing agents) to manifest its ability to promote Schwann cell differentiation. We suggest that ascorbic acid promotes Schwann cell myelin formation by enabling the Schwann cell to assemble a basal lamina, which is required for complete differentiation.
 ...
PMID:Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation. 362 5

Embryonic rat-brain extract contains a collagen-stimulating factor which enhances the production of collagen types I, III, IV and V by cultured rat muscle cells. Here we report on the partial characterization and possible mechanism of action of a low-molecular-mass fraction with ascorbate-like activity isolated from embryonic rat brain extracts. This activity eluted very close to ascorbate when filtered through Bio-Gel P-2 and Sephadex G-10. The peak of biological activity showed properties of a reducing agent. Both the biological and reducing activities were lost when the fraction was treated with the enzyme ascorbate oxidase. This factor enhanced in a time-dependent manner, the secretion of procollagen, pulse-labeled with [3H] proline. Incubation of the muscle cultures with the factor increased by 15-fold the ratio of hydroxyproline to proline residues in secreted macromolecules over controls. A fourfold increase in the above ratio was obtained for the cellular proteins. Crude homogenates from control and factor-stimulated cultures were tested for prolyl hydroxylase activity using [3H](Pro-Gly-Pro)n as a substrate. Cultures treated with the collagen-stimulating factor showed a 5-50-fold increase in prolyl hydroxylation activity compared to controls. No effect on prolyl hydroxylation was found when the factor was added in vitro to either control or stimulated enzyme preparations. Our results suggest that the collagen-stimulating factor contains ascorbate-like activity which promotes the secretion of collagenous proteins by increasing hydroxylation of proline residues in their polypeptide backbone.
 ...
PMID:Collagen-stimulating factor from embryonic brain has ascorbate-like activity and stimulates prolyl hydroxylation in cultured muscle cells. 396 53

A low-molecular-weight factor from embryonic rat brain stimulates collagen production in rat muscle cultures. This effect is associated with increased hydroxylation of proline residues in collagenous proteins produced by the cells. Here, we show that increased hydroxylation (22-and 7.5-fold) was also observed with extracts of rat embryonic spinal cord and extracts of the rat pheochromocytoma cell line PC12. A 5-25-fold stimulation in proline hydroxylation was obtained when muscle cells were cocultured with chick ciliary ganglia or with embryonic rat spinal cord explants. Medium conditioned by rat spinal cord explants also increased prolyl hydroxylation. Incubation of the muscle-nerve cocultures with ascorbate oxidase markedly reduced the observed increase in proline hydroxylation. These results show that the cultured explants release a factor which promotes proline hydroxylation and collagen production by muscle. This factor seems to be ascorbic acid or an ascorbate-like compound.
 ...
PMID:Ciliary ganglia and spinal cord explants release an ascorbate-like compound which stimulates proline hydroxylation and collagen formation in muscle cultures. 404 82