Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cytochemical study was made of some metabolic enzymes in the cerebellar neurons during postnatal ontogenesis after injection of cis-dichlorodiammineplatinum into 10-day-old rats. The profiles during development of neuron-specific enolase immunoreactivity (involved in the glycolytic pathway), dihydrofolate reductase activity (involved in the metabolism of nucleic acids and folate) and dipeptidylaminopeptidase II activity were determined in lobules V-VII of cerebellar vermis. At different developmental stages, treated rats had folia in which the morphology and cytochemical responses of Purkinje neurons were greatly affected. On postinjection day 1 (PD 11), only neuron-specific enolase immunoreactivity was changed, reactions being more intense at the basal pole, which was abnormally enlarged in several neurons. Seven days after treatment (PD 17), the dihydrofolate reductase reaction showed weakly positive cells with small grains of formazan in the perinuclear regions and dipeptidylaminopeptidase II activity, which had appeared at this time in some cells of the controls, was not observed. On PD 25 and PD 35, Purkinje cells, probably undergoing clear degeneration, were negative or very weakly positive in all the reactions. Some tracts of folia had no Purkinje cells. These results suggest that cis-dichlorodiammineplatinum affects the differentiation of Purkinje neurons and interferes first with the glycolytic enzyme and then with some enzymes of the synthetic and catabolic machinery, leading to cellular dysfunction and degeneration.
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PMID:Developmental patterns in the rat cerebellum after cis-dichlorodiammineplatinum treatment. 208 77

Redox regulation of DNA-binding proteins through the reversible oxidation of key cysteine sulfhydryl groups has been demonstrated to occur in vitro for a range of transcription factors. The direct redox regulation of DNA binding has not been described in vivo, possibly because most protein thiol groups are strongly buffered against oxidation by the highly reduced intracellular environment mediated by glutathione, thioredoxin, and associated pathways. For this reason, only accessible protein thiol groups with high thiol-disulfide oxidation potentials are likely to be responsive to intracellular redox changes. In this article, we demonstrate that zinc finger DNA-binding proteins, in particular members of the Sp-1 family, appear to contain such redox-sensitive -SH groups. These proteins displayed a higher sensitivity to redox regulation than other redox-responsive factors both in vitro and in vivo. This effect was reflected in the hyperoxidative repression of transcription from promoters with essential Sp-1 binding sites, including the simian virus 40 early region, glycolytic enzyme, and dihydrofolate reductase genes. Promoter analyses implicated the Sp-1 sites in this repression. Non-Sp-1-dependent redox-regulated genes including metallothionein and heme oxygenase were induced by the same hyperoxic stress. The studies demonstrate that cellular redox changes can directly regulate gene expression in vivo by determining the level of occupancy of strategically positioned GC-binding sites.
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PMID:Physical and functional sensitivity of zinc finger transcription factors to redox change. 862 48