Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cholinergic differentiation factor ciliary neurotrophic factor (CNTF) suppresses noradrenergic properties while inducing cholinergic and peptidergic properties in sympathetic neurons. In the rat, this includes suppression of the noradrenergic enzymes tyrosine hydroxylase and dopamine beta-hydroxylase. Lower enzyme levels result in part from suppression of gene transcription, but the mechanisms are unknown. We found that ciliary neurotrophic factor decreased the transcriptional activator Phox2a in neuroblastoma cells and cultured sympathetic neurons, suggesting that the loss of Phox2a is part of the mechanism by which CNTF suppresses tyrosine hydroxylase and dopamine beta-hydroxylase. Consistent with this model, Phox2a is suppressed in rat cholinergic sympathetic neurons where noradrenergic enzymes decrease, but is not altered in mouse cholinergic neurons where these enzymes remain high.
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PMID:Ciliary neurotrophic factor suppresses Phox2a in sympathetic neurons. 1510 27

The effects of one or five daily intraperitoneal injections of a neurotensin (NT) receptor agonist NT69L (2 mg/kg, i.p.) on the expression of NT (NTS), dopamine 1 and 2 receptors, tyrosine hydroxylase, and DOPA decarboxylase using immunohistochemical and real-time PCR were investigated in rats. Except for the striatum, acute injection of NT69L did not affect neurotensin receptors as compared to saline control. However, 5 daily injections of NT69L resulted in down-regulation of both NTS-1 protein and mRNA levels in several brain regions with the striatum showing a dramatic decrease in NTS-1 expression (P<0.05). The down-regulation of NTS-1 in the striatum, hypothalamus, and substania nigra (SN) after 5 daily injections was confirmed by autoradiography. Acute injection of NT69L increased NTS-2 mRNA and protein level in prefrontal cortex (PFC). NTS-3 mRNA expression and protein levels were slightly down-regulated in hypothalamus, periaqueductal gray (PAG), and SN, though the difference was not significant. The results indicated a difference in the profile of NT receptors expression in response to NT69L. Tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) mRNA was significantly down-regulated in striatum but not in SN. Interestingly, Nurr 1, a transcriptional activator of TH, was dramatically up-regulated in striatum, but down-regulated in PFC, suggesting that different modulating mechanisms may participate in NT69L tolerance in different regions. The present results suggest that distinct NT receptors involved in the effects exerted by NT69L may contribute to the interactions of NT69L with both neural networks and cellular proteins.
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PMID:Effects of 5 daily injections of the neurotensin-mimetic NT69L on the expression of neurotensin receptors in rat brain. 1587 17

The classical progesterone receptors (PRs) are expressed in some hypothalamic dopaminergic and brainstem noradrenergic neurones. Progesterone influences prolactin and luteinising hormone release from the anterior pituitary gland, in part by regulating the activity of these catecholaminergic neurones. The present study aimed to determine the effects of PRs on tyrosine hydroxylase (TH) promoter activity. When CAD, SK-N-SH and CV-1 cells were transfected with TH promoter constructs and PR-A or PR-B expression vectors, progesterone treatment caused three- to six-fold increases in TH-9.0 kb promoter activity in PR-B expressing cells, although only a modest increase or no change in PR-A expressing cells. Using CAD cells, deletional analysis mapped the site of PR action to the -1403 to -1304 bp region of the TH promoter. Mutational analysis of putative regulatory sequences in this region indicated that multiple DNA elements are required for complete PR-B transactivation. Electrophoretic mobility shift assays were unable to demonstrate direct PR-B binding to TH promoter DNA sequences. However, chromatin immunoprecipitation analysis indicated PR-B was recruited to the TH promoter. Two different PR-B DNA binding domain mutants had opposing effects on PR-B-mediated TH promoter activation. A GS to AA mutation located in the p-box of the first zinc finger of PR-B inhibited progesterone transactivation of the TH promoter, whereas a C to A mutation in the zinc finger increased transactivation. PR-A was able to inhibit PR-B transactivation in a dose-dependent manner, although the degree of PR-A inhibition was dependent on the TH promoter deletion construct. These data indicate that ligand-bound PR-B is recruited to DNA elements in the TH promoter and acts as a transcriptional activator of the TH gene, and also that changes in the ratio of PR-A to PR-B may affect the ability of progesterone to increase TH expression.
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PMID:Differential and interactive effects of ligand-bound progesterone receptor A and B isoforms on tyrosine hydroxylase promoter activity. 2181 51