Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolactin stimulates citrate accumulation in prostate cells by increasing the expression of mitochondrial aspartate aminotransferase (mAAT). In this study, we further investigated the mechanism of prolactin regulation of mAAT expression in rat lateral prostate and LNCaP and PC-3 prostate cancer cells. Prolactin and 12-O-tetra-decanoylphorbol 13-acetate (TPA) increased the mAAT mRNA level twofold to fourfold. In addition, prolactin and TPA increased protein kinase C (PKC) activity in prostate cells 20% to 60% and 40% to 210%, respectively. The effects of both prolactin and TPA on mAAT mRNA were eliminated by downregulation of PKC. The effect of prolactin and TPA on gene transcription was determined using mAAT-chloramphenicol acetyltransferase (CAT) reporter-gene constructs, transiently transfected into PC-3 cells. The 59 untranslated region of the precursor form (pmAAT) of the mAAT gene contains five sequences that are homologous to the consensus TPA response elements (TRE). Reporter constructs with various combinations of these sequences were used to assay prolactin stimulation of CAT transcription in PC-3 cells. Prolactin increased CAT expression in PC-3 cells transfected with a reporter gene containing four of the TRE consensus sequences. Another CAT reporter gene, which contained two of the putative TREs, was also stimulated by prolactin, but a third reporter, containing the two other TRE sequences, was not induced by prolactin. These results suggest that prolactin regulates mAAT at the transcriptional level. Moreover, because both prolactin and TPA induced PKC activity, and because the effects of prolactin and TPA were eliminated when PKC was downregulated, we postulate that the prolactin effect on mAAT expression is mediated via the diacylglycerol PKC signal transduction pathway in rat lateral prostate and human prostate cancer cells.
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PMID:Protein Kinase C Mediates Prolactin Regulation of Mitochondrial Aspartate Aminotransferase Gene Expression in Prostate Cells. 1085 Dec 92

Blood samples were taken from the retrobulbar venous plexus or the sublingual vein of male HamIbm:Wist rats to compare clinical pathology parameters between the two sampling techniques. By analogy with a pharmacokinetic study, blood was sampled six times during one day from unfasted animals. After 3 weeks of recovery, blood was taken from fasted animals on a single occasion. In addition, prolactin and corticosterone levels were determined to compare stress-related effects between the two sampling methods. Body weight development and food consumption were similar after single as well as after repeated blood sampling for the two blood sampling techniques. Haemotological evaluation showed a gradual decrease in erythrocyte count, haemoglobin concentration and haematocrit after repeated blood sampling. Repeated withdrawal of blood samples over 24 h corresponding to approximately 22% of the total blood volume resulted in a decrease in red blood cell parameters by up to 30%. The withdrawal of approximately 10% of the total blood volume was associated with a decrease in these parameters by up to 10% and should not be exceeded for animal welfare reasons and to allow a reliable evaluation of data in a study. Repeated blood sampling was associated with an initial decrease in the number of white blood cells, mainly due to a reduction in lymphocytes; white blood cell counts were slightly increased one day after. The decrease in lymphocytes and the increase in neutrophils after repeated sampling were generally slightly more pronounced in the blood from the retrobulbar plexus than from the sublingual vein. Comparison of serum clinical chemistry data showed significantly higher activities of creatine kinase and aspartate aminotransferase in samples from the retrobulbar plexus. These findings suggest a higher degree of tissue damage with blood sampling from the retrobulbar plexus than from the sublingual vein. Despite a large inter-individual variability, higher mean values of prolactin on each occasion and corticosterone after a single sample in fasted animals indicate a higher stress associated with blood sampling from the retrobulbar plexus.
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PMID:Comparison of clinical pathology parameters with two different blood sampling techniques in rats: retrobulbar plexus versus sublingual vein. 1107 55

Citrate accumulation and secretion are physiological functions of the prostate gland that are regulated by testosterone and prolactin. The metabolic pathway for citrate production in the prostate involves the activity of mitochondrial aspartate aminotransferase (mAAT). The expression of mAAT in the prostate is regulated by prolactin through a signal transduction pathway mediated by protein kinase C (PKC). In this report we determined which PKC isoforms are expressed in rat lateral prostate epithelial cells and their activation by prolactin. Eight PKC isoforms are expressed in the ventral and lateral prostate lobes. Although all eight isoforms are expressed, only PKCalpha and PKCvarepsilon were stimulated by prolactin and only in the lateral prostate lobe. Activator protein-1 (AP-1) appears to be the target of prolactin-PKC signaling because prolactin stimulated nuclear protein binding to an AP-1 consensus oligodeoxynucleotide. Moreover, the nuclear binding protein stimulated by prolactin also bound an mAAT oligodeoxynucleotide that contained an AP-1 consensus sequence and which competed for binding with the consensus AP-1 oligodeoxynucleotide. A PKCvarepsilon antisense oligodeoxynucleotide blocked expression of mAAT mRNA. Thus, we conclude that PKCvarepsilon is a specific PKC isoform that mediates via AP-1 the signal for prolactin regulation of mAAT gene expression in rat lateral prostate epithelial cells.
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PMID:Protein kinase C alpha, epsilon and AP-1 mediate prolactin regulation of mitochondrial aspartate aminotransferase expression in the rat lateral prostate. 1116 99

The control and alteration of key regulatory enzymes is a determinant of the reactions and pathways of intermediary metabolism in mammalian cells. An important mechanism in the metabolic control is the hormonal regulation of the genes associated with the transcription and the biosynthesis of these key enzymes. The secretory epithelial cells of the prostate gland of humans and other animals possess a unique citrate-related metabolic pathway regulated by testosterone and prolactin. This specialized hormone-regulated metabolic activity is responsible for the major prostate function of the production and secretion of extraordinarily high levels of citrate. The key regulatory enzymes directly associated with citrate production in the prostate cells are mitochondrial aspartate aminotransferase, pyruvate dehydrogenase, and mitochondrial aconitase. Testosterone and prolactin are involved in the regulation of the corresponding genes associated with these enzymes (which we refer to as "metabolic genes"). The regulatory regions of these genes contain the necessary response elements that confer the ability of both hormones to control gene transcription. In this report, we describe the role of protein kinase c (PKC) as the signaling pathway for the prolactin regulation of the metabolic genes in prostate cells. Testosterone and prolactin regulation of these metabolic genes (which are constitutively expressed in all mammalian cells) is specific for these citrate-producing cells. We hope that this review will provide a strong basis for future studies regarding the hormonal regulation of citrate-related intermediary metabolism. Most importantly, altered citrate metabolism is a persistent distinguishing characteristic (decreased citrate production) of prostate cancer (PCa) and also (increased citrate production) of benign prostatic hyperplasia (BPH). An understanding of the role of hormonal regulation of metabolism is essential to understanding the pathogenesis of prostate disease. The relationships described for the regulation of prostate cell metabolism provides insight into the mechanisms of hormonal regulation of mammalian cells in general.
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PMID:Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells. 1219 95

Cattle grazing tall fescue (Festuca arundinacea Schreb.) often develop fescue toxicosis. This condition is thought to be caused by ergot alkaloids produced by the endophyte Neotyphodium coenophialum. Endophytes from wild tall fescue plants, which do not produce ergot alkaloids, were transferred into the endophyte-free tall fescue germplasm, HiMag. The novel associations also lacked the ability to produce ergot alkaloids. Our objective was to determine whether cattle grazing these novel endophyte associations showed signs of fescue toxicosis. At the Fayetteville, Arkansas location, tester steers (n = 72) were assigned to one of four pasture treatments: endophyte-free HiMag tall fescue (HiMag-); 'Kentucky-31' tall fescue infected with its native, toxic endophyte (KY+); and two novel endophyte-infected tall fescue associations, HiMag4 and HiMag9. At the Mount Vernon, Missouri location, steers (n = 54) were used to test three of the four cultivars (HiMag9 was not tested). Ergot alkaloid concentrations in the forage of HiMag4 and HiMag9 were low or undetectable. Respiration rate, rectal temperature, ADG, and hair scores were measured during the grazing period. Blood was collected via jugular venipuncture and used for prolactin, aspartate aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol, triglyceride, and creatinine analysis. Weight gains by steers grazing HiMag4 and HiMag9 did not differ from those of steers grazing HiMag-, but were greater than gains (P < 0.05) by steers on the KY+ treatment. Steers grazing KY+ had higher (P < 0.05) respiration rates, rectal temperatures, and hair scores than did steers grazing novel endophyte and HiMag- pastures. Prolactin, ALP, cholesterol, LDH, and triglycerides all were suppressed (P < 0.05) in steers grazing KY+ compared with steers grazing novel endophyte and HiMag- pastures. Steers grazing the novel endophyte tall fescues did not suffer from the decreased weight gains and toxicities associated with fescue toxicosis, resulting in enhanced animal production.
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PMID:Growth rate and physiology of steers grazing tall fescue inoculated with novel endophytes. 1503 46

To investigate the consequences of freshwater (FW) transfer, we studied the prolactin (PRL) cDNA sequence and its mRNA expression, and physiological responses in the black porgy (Acanthopagrus schlegeli). We cloned and characterized cDNA encoding its PRL from the pituitary gland. Black porgy PRL cDNA consists of 1492 bp and encodes a protein of 212 amino acids including 24 signal peptides. Reverse transcription-PCR showed the PRL mRNA expression in the pituitary gland. Expression of pituitary gland PRL mRNA was significantly higher during FW acclimation. Furthermore, we studied the stress responses and osmoregulatory abilities of black porgy in changing salinities. Plasma cortisol, glucose, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) significantly increased in the fish immediately after transfer to FW. We also identified significant changes in the fish in terms of plasma ions (Na(+), Cl(-), Ca(2+)) and osmolality during the acclimation period. These results suggests that PRL plays an important role in hormonal regulation in osmoregulatory organs, thereby improving the hyperosmoregulatory ability of black porgy in freshwater.
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PMID:Black porgy (Acanthopagrus schlegeli) prolactin cDNA sequence: mRNA expression and blood physiological responses during freshwater acclimation. 1732 40

The effects of electroconvulsive therapy (ECT) on serum levels of the acute-phase reactant C-reactive protein (CRP) and intracellular enzymes such as alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK), have received little attention. If brain cells are damaged, CK-BB, LDH and AST levels are expected to show (minor) elevations. We measured serum levels of prolactin, AST, ALT, LDH, ALP, CK and CRP before and 5 min, 30 min, 4 h, 1 day, 2 days, and 3 days after ECT in 15 consecutive patients (eight women and seven men; mean 53.9 years old, range 3082) who did not receive ECT in the preceding 2 weeks. Prolactin levels increased (P = 0.001), but none of the other mean concentrations significantly increased over time. All concentrations remained within the normal range in every patient, except for five samples with elevated CK levels (range 333-675 IU/l). CK-MB and CK-BB fractions, however, remained low, indicating that skeletal muscle was the source of the CK elevation. Serum levels of markers of brain cell leakage and inflammation remained low following one ECT session, suggesting that ECT does not cause direct brain cell leakage, nor an inflammatory response.
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PMID:Serum markers of brain-cell damage and C-reactive protein are unaffected by electroconvulsive therapy. 1785 85

It is well established that grazing Neotyphodium coenophialum-infected forages results in reduced BW gain and serum prolactin concentrations of cattle. The objective of this study was to determine the potential effects of toxic endophyte-infected tall fescue consumption on blood metabolites, carcass characteristics, and content of proteins critical for AA metabolism in the liver, kidney, and LM tissue of growing steers. Steers grazed a low toxic endophyte (LE; 0.023 microg/g ergot alkaloids) tall fescue-mixed grass pasture (n = 9; BW = 266 +/- 10.9 kg; 5.7 ha) or a high toxic endophyte (HE; 0.746 microg/g of ergot alkaloids) tall fescue pasture (n = 10; BW = 267 +/- 14.5 kg; 5.7 ha) from June 14 through at least September 11 (> or =89 d). No difference was observed for BW (P < 0.10) for the overall 85-d growth period. Also, no differences were observed for ribeye area/100 kg of HCW (P > 0.91), backfat (P > 0.95), or backfat/100 kg of HCW (P > 0.67). However, ADG (P < 0.01), final BW (P < 0.05), HCW (P < 0.01), dressing percentage (P < 0.01), ribeye area (P < 0.01), whole liver wet weight (P < 0.01), and whole liver wet weight/100 kg of end BW (P < 0.01) were greater for LE steers than HE steers. After 85 d of grazing, serum concentrations of alkaline phosphatase (P < 0.05), alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.03), cholesterol (P < 0.01), lactate dehydrogenase (P < 0.01), and prolactin (P < 0.01) were less for HE than LE steers. At slaughter, hepatic content of cytosolic phosphoenolpyruvate carboxykinase (P < 0.01) was greater in HE steers than LE steers. Hepatic content of aspartate aminotransferase (P < 0.01) also was greater, whereas renal and LM content were not (P > or = 0.42). No differences (P > or = 0.15) were observed for hepatic, renal, and LM content of alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase, and 3 glutamate transport proteins. These data indicate that the HE steers displayed classic endophyte toxicity symptoms for growth and blood variables, classic symptoms that were concomitant with novelly identified altered glucogenic capacity of the liver and decreases in carcass characteristics.
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PMID:Growing steers grazing high versus low endophyte (Neotyphodium coenophialum)-infected tall fescue have reduced serum enzymes, increased hepatic glucogenic enzymes, and reduced liver and carcass mass. 1895 29

Citrate production and accumulation are characteristic physiological functions of the prostate gland that are regulated by testosterone and prolactin. Results reported here show that treatment of LNCaP cells with dihydrotestosterone (DHT) resulted in increased intracellular citrate and increased citrate accumulation in the medium. Moreover, DHT also caused an increase in both mitochondrial aspartate aminotransferase (mAAT) activity and the steady state level of pmAAT (precursor) mRNA. Androgen treatment increased the rate of citrate oxidation by LNCaP cells as it does in rat ventral prostate which suggests that DHT increased aconitase activity in LNCaP cells. The results reported here are consistent with the operation of the glutamate-aspartate-citrate pathway that we described for rat ventral prostate. In addition, these results provide the first evidence that androgen responsive functions associated with citrate metabolism are retained in LNCaP cells. In addition, and more important, these results suggest that the more aggressive PC-3 carcinoma cell line has a higher rate of citrate oxidation than the less aggressive LNCaP cell line. This could have significant implications for our understanding of the relationship between alterations in prostate citrate metabolism and expression of the malignant phenotype.
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PMID:Regulation of citrate metabolism by androgen in the LNCaP human prostate carcinoma cell line. 2115 39

Continuous dopaminergic stimulation (CDS) has been an important strategy of drug development for the treatment of Parkinson's disease (PD). Rotigotine is a non-ergoline D3/D2/D1 dopamine agonist for treating PD. As a new treatment option for CDS, rotigotine-loaded microspheres (RoMS), a long-acting sustained-release microspheres for injection with poly(lactide-co-glycolide) as drug carrier, are now being evaluated in clinical trial. In this study, subchronic toxicity of RoMS in SD rats has been characterized via intramuscular administration with RoMS (0-240 mg/kg/week) on a consecutive weekly dosing schedule for 3 months followed by 1-month recovery period. The No Observed Adverse Effect Level (NOAEL) was 45 mg/kg/week. One male at 240 mg/kg died from an extensive pulmonary embolism. The major toxicological effects were associated with the dopamine agonist-related pharmacodynamic properties of rotigotine (e.g. hyperactivity and stereotype, enlarged ovary, sporadic gastric mucous membrane lesions, decreased body weight, food consumption and prolactin, and increased mononuclear cell, neutrophil granulocyte, aspartate aminotransferase and alanine aminotransferase) and foreign body removal reaction induced by poly(lactide-co-glycolide) and carboxymethycellulose sodium. At the end of recovery period, all findings had recovered to a normal level or to a certain degree except foreign body reaction at injection sites. RoMS has exhibited high safety on SD rats.
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PMID:Three-month subchronic intramuscular toxicity study of rotigotine-loaded microspheres in SD rats. 2345 7


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