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)

The mechanism of [3H]dopamine [( 3H]DA) release was investigated using primary cultures of dispersed cells from the rat tuberoinfundibular region, which contains tyrosine hydroxylase (TH)-like immunoreactive neurons. The calcium ionophore A23187 at 10 nM and above caused a significant and dose-dependent increase in [3H]DA release. In the presence of 50 microM A23187, [3H]DA release was detectable within 30 s and reached a plateau in 15 min. The induction of [3H]DA release by 50 microM A23187 was abolished by lowering the extracellular calcium concentration with 2 mM EDTA. Maitotoxin, another calcium-channel activator, also increased [3H]DA release at a concentration of 50 ng/ml. Exogenous additions of 100 mIU/ml phospholipase A2 and 10 microM arachidonate caused significant release of [3H]DA. Furthermore, A23187 stimulated [3H]arachidonate release from tuberoinfundibular dopaminergic (TIDA) neurons in a dose- and time-dependent manner. These results suggest that extracellular calcium and arachidonate are involved in the process of [3H]DA release from rat TIDA neurons.
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PMID:Involvement of extracellular calcium and arachidonate in [3H] dopamine release from rat tuberoinfundibular neurons. 257 91

Rat striatal tyrosine hydroxylase can be isolated in both a soluble and a synaptic membrane-bound form. The membrane-bound enzyme, which exhibits lower Kms for both tyrosine (7 microM) and reduced pterin cofactor (110 microM) relative to the soluble enzyme (47 microM and 940 microM, respectively), can be released from the membrane fraction with mild detergent, and concomitantly its kinetic properties revert to those of the soluble enzyme. Treatment of membrane-bound tyrosine hydroxylase with C. perfringens phospholipase C increased the Km of the enzyme for tyrosine to 27 microM and the Vmax by 60% without changing the Km for cofactor. In contrast, treatment of membrane-bound tyrosine hydroxylase with V. russelli phospholipase A2 increased the Km for tyrosine to 48 microM, increased the Vmax, and increased the Km for cofactor to 560 microM. The enzyme remained bound to the membrane fraction following both phospholipase treatments. Addition of phospholipids to treated enzyme could partially reverse the effects of phospholipase A2 treatment, but not the effects of phospholipase C treatment. The kinetic properties of phospholipase-treated, detergent-solubilized tyrosine hydroxylase were identical to those of the control solubilized enzyme. Tyrosine hydroxylase appears to interact with synaptic membrane components to produce at least two separately determined consequences for the kinetic properties of the enzyme.
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PMID:Effects of phospholipases on the kinetic properties of rat striatal membrane-bound tyrosine hydroxylase. 613 Nov 7

Phospholipase A2 is a calcium-dependent enzyme which produces membrane fusogens. The possibility that it may be involved in exocytosis of catecholamine from primary dissociated cultures of bovine adrenal medullary cells was investigated by studying the effects on catecholamine secretion and 44Ca2+ uptake of three phospholipase A2 inhibitors: p-bromophenacyl bromide (BPB), Upjohn Compound 1002, and mepacrine. The three compounds completely inhibited catecholamine secretion induced by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), elevated K+, and Ba2+. The inhibition of nicotinic agonist-induced secretion by mepacrine may have been caused by direct nicotinic antagonist activity of the drug. The phospholipase inhibitors also inhibited 45Ca2+ uptake into the cells stimulated by DMPP and elevated K+. Inhibition of 45Ca2+ uptake and catecholamine secretion exhibited identical dose-response curves. Other effects of the inhibitors were also investigated. Compound 1002 had no effect on 45Ca2+ efflux from the cells in the presence of either normal or reduced Na+ concentrations. BPB inhibited DMPP-stimulated phosphorylation of tyrosine hydroxylase which, like exocytosis, is dependent on a rise in cytosolic Ca2+. The data suggest that phospholipase A2 inhibitors block catecholamine secretion from intact chromaffin cells by blocking Ca2+ influx.
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PMID:Phospholipase A2 inhibitors block catecholamine secretion and calcium uptake in cultured bovine adrenal medullary cells. 686 4

The cytotoxicity of beta-bungarotoxin (beta-BTX), a snake venom neurotoxin with phospholipase A2 activity, for chick neurons was investigated using organ and monolayer cultures of retina. Beta-BTX led to a marked reduction in the total activities of choline acetyltransferase and glutamate decarboxylase of retina cultures at concentrations as low as 100 pM. The total activity of lactate dehydrogenase was, however, much less affected by beta-BTX. Also, the total activity of tyrosine hydroxylase of organ-cultured retina decreased only at 30-50 fold higher concentrations of the toxin. The total activity of the glial marker glutamine synthetase was not changed by beta-BTX. In contrast to this selectivity for neurons displayed by beta-BTX, non-neurotoxic phospholipases A2 from bee venom and porcine pancreas led to a simultaneous loss of both neuronal and glial marker enzymes. Light and electron microscopy of organ-cultured retina showed that only cells in the ganglion cell layer and the inner third of the amacrine cell layer degenerated after incubation with beta-BTX. In the toxin-sensitive cells, the Golgi apparatus and the endoplasmatic reticulum appeared the first subcellular structures to be affected. It is concluded that beta-BTX preferentially recognizes and/or destroys cholinergic and GABAergic cells in the amacrine and ganglion cell layers of the developing chick retina. This toxin may thus be a useful probe to investigate cell surface properties of cholinergic and GABAergic neurons in the chick central nervous system.
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PMID:Beta-bungarotoxin-induced cell-death of neurons in chick retina. 717 91

Exoenzyme S (ExoS), which has been implicated as a virulence factor of Pseudomonas aeruginosa, catalyzes transfer of the ADP-ribose moiety of NAD+ to many eukaryotic cellular proteins. Its preferred substrates include Ras and several other 21- to 25-kDa GTP-binding proteins. ExoS absolutely requires a ubiquitous eukaryotic protein factor, termed FAS (factor activating ExoS), for enzymatic activity. Here we describe the cloning and expression of a gene encoding FAS from a bovine brain cDNA library and demonstrate that purified recombinant FAS produced in Escherichia coli activates ExoS in a defined cell-free system. The deduced amino acid sequence of FAS shows that the protein (245 residues, calculated molecular mass 27,743 Da) belongs to a highly conserved, widely distributed eukaryotic protein family, collectively designated as 14-3-3 proteins. Various functions have been reported for members of the 14-3-3 family, including phospholipase A2 activity and regulation of tyrosine hydroxylase, tryptophan hydroxylase, and, possibly, protein kinase C activities. Identification of FAS as a 14-3-3 protein establishes an additional function for this family of proteins--the activation of an exogenous ADP-ribosyltransferase. Elucidation of the precise role of FAS in activating ExoS will contribute to understanding the molecular mechanisms by which P. aeruginosa causes disease.
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PMID:The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. 846 Jan 41

Cytidine-5'-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of citicoline that are responsible for its effectiveness. Our studies in transient cerebral ischemia suggest that citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii) preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi) restoring Na(+)/K(+)-ATPase activity. These observed effects of citicoline could be explained by the attenuation of phospholipase A(2) activation. Based on these findings, a singular unifying mechanism has been hypothesized. Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release.
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PMID:Citicoline: neuroprotective mechanisms in cerebral ischemia. 1179 39

Ubiquitin, a small protein consisting of 76 amino acids, acts in protein degradation, DNA repair, signal transduction, transcriptional regulation, and receptor control through endocytosis. Using proteomics, we compared the differentially ubiquitinated proteins between a deltamethrin-resistant (DR) strain and a deltamethrin-sensitive (DS) strain in third-instar larvae of the diamondback moth. We used polyubiquitin affinity beads to enrich ubiquitinated proteins and then performed one-dimensional SDS-PAGE separation and mass spectrometric identification. In the DR strain, We found 17 proteins that were upregulated (relative to the DS strain), including carbonic anhydrase family members, ADP ribosylation factor 102F CG11027-PA, protein kinase 61C, phospholipase A2 , dihydrolipoamide dehydrogenase, tyrosine hydroxylase, and heat shock proteins, and five proteins that were downregulated in the DS strain, including carboxylesterase and DNA cytosine-5 methyltransferase. These results were also verified by qPCR. The differentially ubiquitinated proteins/enzymes were mainly responsible for protein binding, catalytic activity, and molecular transducer activity. These results improve our understanding of the relationship between protein ubiquitination and the deltamethrin stress response.
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PMID:PROTEOMIC ANALYSIS OF UBIQUITINATED PROTEINS FROM DELTAMETHRIN-RESISTANT AND SUSCEPTIBLE STRAINS OF THE DIAMONDBACK MOTH, Plutella Xylostella L. 2598 7