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

Transgenic mice containing an upstream glucokinase (betaGK) promoter- simian virus 40 T antigen (Tag) fusion gene develop neuroendocrine tumors primarily in the pancreas, gut, and pituitary. Pancreatic tumors from a line with delayed tumorigenesis were of two different types: insulinomas and noninsulinomas. The noninsulinomas are often periductal in location, express none of the four major islet peptide hormones, Glut-2, Pdx1, tyrosine hydroxylase, Pax4, Pax6, or Nkx6.1, but do express glucokinase, Sur1, Isl1, Hnf3beta, Hnf6, Beta2/NeuroD, and Nkx2.2. Cells from two different noninsulinoma tumors, when adapted to culture, began to express either insulin, glucagon, or somatostatin. Given the partial gene expression repertoire of the noninsulinoma tumors, their apparent periductal origin, and the ability of these cells to partially cytodifferentiate in culture, we suggest that these tumors are derived from islet progenitor cells. Thus, betaGK-Tag transgenic mice provide a new model system for studying the events that occur during both islet cell neogenesis and normal embryonic development.
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PMID:Targeted oncogenesis of hormone-negative pancreatic islet progenitor cells. 967 33

During neurodegenerative processes, cascades of degeneration and subsequent regeneration are triggered. However, the molecular nature of the factors involved in the neurodegeneration of the CNS remains largely unknown. In this study, the variations of protein expression in the striatum of adult Sprague-Dawley rats following 6-hydroxydopamine lesions were investigated, in order to better understand the molecular events occurring in the denervated target tissue. The rat striatum, ipsilateral to the lesion was analysed by two-dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization-time of flight mass spectrometry. Seven proteins were up-regulated (188.1-750% compared to control) in response to the lesion: amyloid precursor-like protein 2 (APLP2), kininogen, glucokinase, tropomyosin alpha chain, type brain-1 and calpactin I light chain; whilst four proteins, neural epidermal growth factor-like 2, minichromosome maintenance 6, and thyroid hormone receptor beta-2, were down-regulated (to between 36% and 59% of levels in sham-operated controls). Three proteins that did not match with available data in the SWISS-PROT protein database were also determined. Immunohistochemical analysis demonstrated colocalization of APLP2 and tyrosine hydroxylase in the nigral neurons. Moreover, reduction of APLP2-positive neurons in the substantia nigra pars compacta as well as the increases in the substantia nigra pars reticulata and in the striatum were observed. Furthermore, the conditioned medium of the Chinese hamster ovary cells over-expressing APLP2-751 (chondroitin sulphate-modified), but not APLP2-763 (nonchondroitin sulphate-modified), was able to increase the number of the tyrosine hydroxylase-positive neurons in fetal mesencephalic cultures. These results suggest that the expression of APLP2, a protein that has been thought to be associated with Alzheimer's disease, is up-regulated in the striatum following dopaminergic denervation. They also support the view that chondroitin sulphate-modified APLP2 protein may play an important role in the dopaminergic nigrostriatal system.
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PMID:Identification and comparative analysis of differentially expressed proteins in rat striatum following 6-hydroxydopamine lesions of the nigrostriatal pathway: up-regulation of amyloid precursor-like protein 2 expression. 1237 26

The neurochemical phenotype(s) of metabolic sensing neurons in the dorsal vagal complex (DVC) remains unclear. These studies utilized single-cell quantitative real-time RT-PCR, in conjunction with laser-catapult microdissection, to address the hypothesis that DVC A2 neurons express genes that encode the characterized metabolic transducers, e.g. glucokinase (GCK) and the energy-dependent potassium channel, K(ATP). Studies show that either glucose or lactate alters synaptic firing of DVC chemosensory neurons, and that delivery of the latter fuel into the caudal hindbrain amplifies insulin-induced hypoglycemia (IIH) and elevates neuronal glucose and monocarboxylate transporter, GCK, and sulfonylurea-1 mRNA in the DVC. We thus examined the additional premise that IIH modifies A2 substrate transporter and metabolic transducer gene profiles, and that such transcriptional responses may be reversed by exogenous lactate and/or glucose. Individual tyrosine hydroxylase (TH)-immunoreactive (-ir) A2 neurons were microdissected from the caudal DVC 2 h after injection of insulin or saline, and continuous caudal fourth ventricular (CV4) infusion of lactate, glucose, or artificial cerebrospinal fluid. The data show that IIH decreased MCT2, but elevated GLUT3, GLUT4, GCK, and SUR-1 transcripts in A2 neurons. Blood glucose levels in insulin-injected rats were further reduced by CV4 infusion of either lactate or glucose. Lactate plus insulin reversed hypoglycemic reductions in MCT2 mRNA and further augmented GLUT3 transcripts in A2 neurons, whereas glucose infusion in insulin-injected rats further increased GLUT3 and GCK gene profiles. The present results demonstrate that caudal DVC A2 neurons express molecular markers for metabolic sensing, and genes that encode glucose and monocarboxylate transporters. Evidence that IIH reduces A2 MCT2, but elevates GLUT3 and GLUT4 gene profiles suggests that glucose may be a primary energy source to these cells during hypoglycemia, while decreased lactate uptake, alone or relative to glucose uptake, may be a critical manifestation of systemic glucose deficiency at the cellular level. Findings that singular fuel repletion does not normalize hypoglycemic patterns of glucose transporter, GCK, or SUR-1 mRNA expression in A2 neurons imply that sufficient supply of both energy substrates is required for metabolic balance, and that cellular adaptation to the prevalence of either fuel may increase cellular dependence on glucose-specific metabolites or other products.
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PMID:In situ coexpression of glucose and monocarboxylate transporter mRNAs in metabolic-sensitive caudal dorsal vagal complex catecholaminergic neurons: transcriptional reactivity to insulin-induced hypoglycemia and caudal hindbrain glucose or lactate repletion during insulin-induced hypoglycemia. 1974 43