Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detailed study of developmental changes in the enteric nervous system is necessary to disclose the pathogenesis of Hirschsprung's and allied disease, some of which have hypoplastic ganglia. Therefore experiments were undertaken to study the fate of neural crest cells that develop in the rat gut during ontogeny. A polyclonal antibody against ret proto-oncogene product (c-Ret protein) and various monoclonal antibodies against neural markers (tyrosine hydroxylase, dopamine beta hydroxylase, microtubule-associated protein 5, microtubule-associated protein 2 and 160-kd neurofilaments) were used to identify neural crest-derived cells in rat embryos (10.5 to 15.5 days' gestation) and adult rats using a double immunostaining method. C-Ret protein was an early marker of lineage determination in the development of the enteric nervous system (11.5-day embryo: E 11.5). C-Ret-positive cells transiently coexpressed tyrosine hydroxylase, which also was observed in the vagal crest-derived precursors of enteric neurons (days E 11.5 to E 13.5). These cells also coexpressed other neural markers in the proximal gut. Expression of neural markers migrated to the distal intestine during development. This study found a discrepancy between the time when these markers appeared in the cranial and when they appeared in the caudal intestine. Tyrosine hydroxylase-positive cells did not appear in the postumbilical gut. The formation of the primitive neural network in the entire myenteric plexus at day E 15.5 was demonstrated by c-Ret protein. Other neural markers were lost or bad decreased immunoreactivity throughout the entire intestine of the E 15.5 and adult animals. In conclusion, (1) c-Ret protein is one of the earliest markers of lineage determination in the development of the enteric nervous system, (2) each neural marker is expressed at its own time and differs in spatial developmental lineage, (3) c-Ret protein and other neural markers are transiently expressed by a particular group of neural cells during the embryonic period, (4) there is a subpopulation of cells that has never transiently expressed tyrosine hydroxylase in the postumbilical gut, which may have originated from tissue other than the vagal crest, and (5) the primitive neural network in the myenteric plexus was completed at day E 15.5.
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PMID:ret Proto-oncogene product is a useful marker of lineage determination in the development of the enteric nervous system in rats. 902 62

The role of glial cell line-derived neurotrophic factor (GDNF) in the survival of dopaminergic neurons has been well documented, but its effect on dopamine biosynthesis remains to be elucidated. In this study, the effect of GDNF on the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis, was investigated. We found that GDNF elevated the expression of the TH gene at both mRNA and protein levels in TGW cells, a human neuroblastoma cell line. GDNF significantly enhances the transcription rate of the TH gene as actinomycin D prevented the induction of TH mRNA and GDNF increased the activity of the TH promoter. In addition, GDNF exerts a relatively weak but significant effect on the stability of TH mRNA, because GDNF delayed the degradation of TH mRNA and strengthened a special TH mRNA/protein interaction known to be relevant with TH mRNA stability. By comparing several human neurogenic cell lines, we found that GDNF-induced TH expression was only observed in the cells possessing Ret protein and coincided with the expression levels. Taken together, these results indicate that GDNF up-regulates the expression of the TH gene by promoting the transcription of the TH gene and the stability of TH mRNA with the Ret receptor dependency in some neuroblastoma cell lines. Thus, GDNF exerts its neurotrophic role not only in promoting cells survival, but also in affecting dopamine biosynthesis.
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PMID:Glial cell line-derived neurotrophic factor up-regulates the expression of tyrosine hydroxylase gene in human neuroblastoma cell lines. 1235 85