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)

Cadmium, in addition to producing a variety of toxic manifestations, is known to accumulate in certain "target" organs which include liver and kidney where histological and functional damage becomes apparent. The daily intraperitoneal injection of cadmium chloride for 21 or 45 days stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1, 6-diphosphatase and glucose-6-phosphatase elevated blood glucose and urea, and lowered hepatic glycogen in rats. Whereas chronic Cd treatment failed to alter adenosine-3', 5'-monophosphate phosphodiesterase (PDE) activity, cyclic AMP (cAMY and the activity of basal and fluoride-stimulated forms of hepatic adenylate cyclase (AC) were markedly increased. However, the cAMP binding to hepatic protein kinase was decreased as was the kinase activity ration. An acute dose of Cd decreased hepatic glycogen content and increased blood glucose, serum urea, and hepatic cAMP. Chronic exposure to Cd induced adrenal hypertrophy and augmented adrenal norepinephrine and epinephrine as well as the activity of adrenal tyrosine hydroxylase. This treatment decreased prostatic and testicular weights of mature rats. Although cAMP as well as AC activity of the prostate gland were reduced, cAMP binding to the prostatic protein kinase was increased as was the activity of the cAMP-dependent form of the enzyme. Testicular AC and PDE activities, however, were stimulated, although cAMP remained unaffected. Whereas the activities of the cAMP-dependent and the independent forms of testicular protein kinase were significantly depressed, the binding of cAMP to protein kinase from testes of Cd-treated rats was not affected. In most cases, the observed metabolic alterations persisted up to 28 days on cessation of Cd administration. Subacute Cd treatment suppressed pancreatic function as evidenced by lowered serum immunoreactive insulin (IRI) in presence of hyperglycemia, as well as by partial inhibition of phentolamine-stimulated increases in serum IRI. Although chronic Cd treatment failed to alter the concentration of brain stem norepinephrine and cerebrocortical acetylcholine esterase activity, serotonin levels of brain stem were depressed and the concentration of striatal dopamine and cerebrocortical acetylcholine were significantly elevated when compared with the values seen in control nonexposed animals.
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PMID:Aspects of the biochemical toxicology of cadmium. 17 84

Transcripts encoded by 2 different rat genomic clones, rg13 and rg100, appear to be typical brain-specific polyA- RNAs, as defined by previous criteria (rare, polysomal, and postnatally expressed from single-copy genes). However, we have found by using a sensitive nuclease protection assay that low levels of these transcripts (10% and 3%, respectively) are detected in polyA+ RNA. To determine if rg transcripts that fractionate as polyA- could have resulted from nicking of polyA+ RNA, we assessed the integrity of 2 known polyA+ RNAs, those of tyrosine hydroxylase, a 2-kilobase (kb) mRNA, and sodium channel, a 9.5-kb RNA. Using RNA prepared by several different procedures, including LiCl-urea and guanidine thiocyanate followed by CsCl centrifugation, the shorter message fractionated as polyA+ after 2 cycles over oligodeoxythymidine (oligo-dT) cellulose, whereas the majority of the longer sodium channel RNA fractionated as polyA, as assayed by nuclease protection using probes from the 5' end of the 2 genes. However, on Northern blots, the same RNA preparations showed an intact 9.5-kb sodium channel band only in polyA+ RNA, suggesting that the polyA- RNAs were randomly cleaved, resulting in a smear of sizes that could not be detected as a discrete band. These data imply that long messages may be nicked during standard isolation procedures and that this would not be detected by Northern blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Brain-specific polyA- transcripts are detected in polyA+ RNA: do complex polyA- brain RNAs really exist? 170 66

Intact secretory granules isolated from bovine adrenal medulla express tyrosine hydroxylase (TH) activity. Granule-associated TH sediments on continuous sucrose gradients with dopamine beta-hydroxylase, a marker for granule membranes, indicating that TH is associated with chromaffin granules. Membranes prepared from lysed granules retain TH, whereas granule contents are free of the enzyme. TH immunoreactivity was detected in granule membranes by immunoblot analysis using a polyclonal antiserum against TH. TH immunoreactivity cannot be removed from membranes by washes in high ionic strength buffers and is only partially removed from membranes by treatment with either urea or Na2CO3. TH can be removed from granule membranes by the detergents Nonidet P-40, Triton X-100, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Treatment of membranes with a phosphatidylinositol-specific phospholipase C did not remove TH, ruling out the possibility of a glycosyl phosphatidyl anchor. Fractionation of granule membranes by temperature-induced phase separation in Triton X-114 revealed that TH is recovered in phases in which integral (detergent phase) and hydrophobic (phospholipid phase) membrane proteins are typically found. By contrast, TH from adrenal cytosol fractionated exclusively into the aqueous phase along with other soluble proteins. Digestion of granules with various protease enzymes revealed that TH is resistant to degradation, suggesting that the enzyme is embedded within membranes. TH becomes phosphorylated when intact granules are exposed to the catalytic subunit of the cAMP-dependent protein kinase, indicating that at least the N-terminal region of TH is exposed on the cytoplasmic surface of granules. These results establish that a fraction of TH is an integral component of bovine granule membranes. The association of TH with granule membranes may play a role in coordinating TH activity and catecholamine release.
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PMID:Tyrosine hydroxylase in secretory granules from bovine adrenal medulla. Evidence for an integral membrane form. 196 7

Tyrosine hydroxylase [L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2](TH) was purified from bovine corpus striatum. The purification involved sequential DEAE cellulose, hydroxylapatite and CM Sephadex C-50 chromatography, followed by glycerol density gradient centrifugation. Final preparations appeared to be 90 to 100% pure as judged by polyacrylamide gel electrophoresis under denaturing conditions in acetic acid-urea. The enzyme was estimated to have a minimum molecular weight of approximately 60,000 daltons. Purified TH could be activated in vitro by incubation with magnesium adenosine triphosphate and the catalytic subunit of cyclic AMP-dependent protein kinase (ATP/protein phosphotransferase; EC 2.7.1.37). When the final purified preparation of TH was incubated under these conditions utilizing [gamma-32P]ATP, it was found to incorporate 0.7 to 0.9 mol of phosphorus/mol of protein. These results suggest that the activation of TH in the presence of phosphorylating conditions is due to its phosphorylation by cyclic AMP-dependent protein kinase.
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PMID:Tyrosine hydroxylase: studies on the phosphorylation of a purified preparation of the brain enzyme by the cyclic AMP-dependent protein kinase. 611 Jul 71

A 6M urea-insoluble form of tyrosine hydroxylase (THi) was detected in PC12 pheochromocytoma cells by western blotting immunodetection methods, and the characteristics and mechanisms of formation of this insoluble species were investigated. THi accounts for about 4% of the immunodetectable tyrosine hydroxylase in exponentially dividing pheochromocytoma cells. It is unlikely that a subpopulation of dead or dying cells is the source of THi since essentially no changes in THi levels were detected when cell death was intentionally increased. To measure the kinetics of formation of cellular THi, exponentially dividing cells were metabolically labeled first with [3H]leucine and then with [14C]leucine, and though both 3H and 14C were incorporated into soluble tyrosine hydroxylase, the near absence of 14C in THi demonstrated that a lag period of at least a day exists between biosynthesis of tyrosine hydroxylase and the accumulation of measurable THi. The cellular accumulation of THi can evidently be regulated by the cell, since upon nerve growth factor (NGF) treatment of cells the total content of tyrosine hydroxylase increased and the content of THi decreased to yield, overall, a fivefold lower proportion of THi after 4 days. A large increase in urea-insoluble enzyme was found upon sublethal exposure of cells to ferrous ion and hydrogen peroxide, indicating that oxidative damage via metal-ion-catalyzed formation of hydroxide free radical can yield an enzyme that is similar in its insolubility to THi.
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PMID:A denaturant-insoluble form of tyrosine hydroxylase in PC12 pheochromocytoma cells. 859 May 95

We investigated the proteome of the anterior pituitary gland (AP) in a species in which the genome has been sequenced. Subcellular fractions of APs from 2-month-old male mice were prepared for protein denaturation, treatment with trypsin and analyses utilizing micro liquid chromatography tandem mass spectrometry and the database search software SEQUEST. In the nuclear, non-nuclear 100,000 g and cytosolic fractions, we identified 49, 36 and 68 different proteins, respectively. A total of 115 distinct proteins were detected. We identified growth hormone, prolactin, pro-opiomelanocortin, the alpha-subunit for the glycoprotein hormones, and luteinizing hormone-beta. Groups of other identified proteins included hormone-processing, secretion granule-associated, non-hormonal endoplasmic reticulum-associated, calcium-binding, protein kinase C-associated, histones, non-histone chromosomal, other RNA-binding, heterogeneous nuclear ribonucleoproteins, splicing factors, helicases, lamins, ribosomal, microtubule-associated, microfilament-associated, adenosine triphosphate- and guanosine triphosphate-associated, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation, enzymes in glycolysis and the tricarboxylic and urea cycles and the pentose phosphate path, heat-shock, glutathione-associated, peroxidases, ubiquitin-associated, catabolic, protease inhibitors, other, and blood proteins. The 115 proteins reported in this study and the 145 proteins reported in a previous study on the AP of the adult male Golden Syrian hamster are compared and form a foundation for defining the proteome in normal adult male AP.
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PMID:Mouse anterior pituitary gland: analysis by ion trap mass spectrometry. 1610 33

Aquaporins are a family of water channels found in animals, plants, and microorganisms. A subfamily of aquaporins, the aquaglyceroporins, are permeable for water as well as certain solutes such as glycerol, lactate, and urea. Here we show that the brain contains two isoforms of AQP9--an aquaglyceroporin with a particularly broad substrate specificity--and that the more prevalent of these isoforms is expressed in brain mitochondria. The mitochondrial AQP9 isoform is detected as an approximately 25 kDa band in immunoblots. This isoform is likely to correspond to a new AQP9 mRNA that is obtained by alternative splicing and has a shorter ORF than the liver isoform. Subfractionation experiments and high-resolution immunogold analyses revealed that this novel AQP9 isoform is enriched in mitochondrial inner membranes. AQP9 immunopositive mitochondria occurred in astrocytes throughout the brain and in a subpopulation of neurons in the substantia nigra, ventral tegmental area, and arcuate nucleus. In the latter structures, the AQP9 immunopositive mitochondria were located in neurons that were also immunopositive for tyrosine hydroxylase, as demonstrated by double labeling immunogold electron microscopy. Our findings suggest that mitochondrial AQP9 is a hallmark of astrocytes and midbrain dopaminergic neurons. In physiological conditions, the flux of lactate and other metabolites through AQP9 may confer an advantage by allowing the mitochondria to adjust to the metabolic status of the extramitochondrial cytoplasm. We hypothesize that the complement of mitochondrial AQP9 in dopaminergic neurons may relate to the vulnerability of these neurons in Parkinson's disease.
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PMID:Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane. 1612 13

In this study, we investigated the role of orexinergic systems in dopamine-related behaviors induced by the mu-opioid receptor agonist morphine in rodents. Extensive coexpression of tyrosine hydroxylase with orexin receptors was observed in the mouse ventral tegmental area (VTA). The levels of dopamine and its major metabolites in the nucleus accumbens were markedly increased by the microinjection of orexin A and orexin B into the VTA. The subcutaneous morphine-induced place preference and hyperlocomotion observed in wild-type mice were abolished in mice that lacked the prepro-orexin gene. An intra-VTA injection of a selective orexin receptor antagonist SB334867A [1-(2-methylbenzoxazol-6-yl)-3-[1.5]naphthyridin-4-yl urea] significantly suppressed the morphine-induced place preference in rats. Furthermore, the increased level of dialysate dopamine produced by morphine in the mouse brain was significantly decreased by deletion of the prepro-orexin gene. These findings provide new evidence that orexin-containing neurons in the VTA are directly implicated in the rewarding effect and hyperlocomotion induced by morphine through activation of the mesolimbic dopamine pathway in rodents.
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PMID:Direct involvement of orexinergic systems in the activation of the mesolimbic dopamine pathway and related behaviors induced by morphine. 1640 35

The role of hypocretin (orexin; hcrt/orx) neurons in regulation of arousal is well established. Recently, hcrt/orx has been implicated in food reward and drug-seeking behavior. We report here that in male rats, Fos immunoreactivity (ir) in hcrt/orx neurons increases markedly during copulation, whereas castration produces decreases in hcrt/orx neuron cell counts and protein levels in a time course consistent with postcastration impairments in copulatory behavior. This effect was reversed by estradiol replacement. Immunolabeling for androgen (AR) and estrogen (ER alpha) receptors revealed no colocalization of hcrt/orx with AR and few hcrt/orx neurons expressing ER alpha, suggesting that hormonal regulation of hcrt/orx expression is via afferents from neurons containing those receptors. We also demonstrate that systemic administration of the orexin-1 receptor antagonist SB 334867 [N-(2-methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl urea] impairs copulatory behavior. One locus for the prosexual effects of hcrt/orx may be the ventral tegmental area (VTA). We show here that hcrt-1/orx-A produces dose-dependent increases in firing rate and population activity of VTA dopamine (DA) neurons in vivo. Activation of hcrt/orx during copulation, and in turn, excitation of VTA DA neurons by hcrt/orx, may contribute to the robust increases in nucleus accumbens DA previously observed during male sexual behavior. Subsequent triple immunolabeling in anterior VTA showed that Fos-ir in tyrosine hydroxylase-positive neurons apposed to hcrt/orx fibers increases during copulation. Together, these data support the view that hcrt/orx peptides may act in a steroid-sensitive manner to facilitate the energized pursuit of natural rewards like sex via activation of the mesolimbic DA system.
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PMID:A role for hypocretin (orexin) in male sexual behavior. 1736 Sep 5

Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus.
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PMID:Protective effect of ginsenoside against acute renal failure and expression of tyrosine hydroxylase in the locus coeruleus. 1924 9


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