Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A plasma membrane fraction from Malpighian cells has been isolated by differential and density gradient centrifugation of a pig epidermal homogenate. It was enriched in the marker enzymes 2-naphthylamidase, 5'-nucleotidase, phosphodiesterase I and acid phosphatase and depleted of NADH-ferricyanide reductase and cytochrome c oxidase. It had a protein to lipid ratio of 3:2 by weight. The protein composition was complex with compounds ranging from a molecular weight of 150,000 down to 13,000. Major components with molecular weights 120,000 to 90,000 were glycoproteins. Two other components had molecular weights of 39,000 (actin ?) and 24,000. There were minor components with molecular weights from 63,000 to 46,000. About 76% of the total lipid was present as phospholipid, which was enriched in sphingomyelin. Most of the neutral lipids were accounted for by cholesterol, triacylglycerols and fatty acids: very little glycosphingolipid was present. The preparation was probably derived from non-desmosomal areas of the plasma membrane of Malpighian cells, as desmosomes were not seen in the preparation.
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PMID:The plasma membrane of Malpighian cells from pig epidermis: isolation and lipid and protein composition. 743 17

The metabolism of androgens in prostatic carcinoma has not been sufficiently studied so far, mainly because of the difficulty in obtaining human tissue specimens. The availability of LNCaP (lymph node carcinoma of the prostate) cells which retain most of the characteristics of the original carcinoma (dependence on androgens, presence of androgen receptors, production of acid phosphatase, etc.) has allowed the present in vitro study designed to characterize the metabolic pathways through which testosterone (T) is metabolized in malignant cells. LNCaP cells have been incubated in the presence of different labelled androgenic precursors to quantitate the formation of the respective metabolites, as indicators of the specific activities of the enzymes involved in such conversions; whenever possible, the kinetic constants (Km and Vmax) of the enzymes have also been calculated. It has been observed that, when [14C] T is used as substrate, the cells form both dihydrotestosterone (DHT) and androst-4-en-3,17 dione (delta 4) with the prevalence of the latter. When [14C] delta 4 is the substrate, T and 5 alpha-androstan-3,17-dione (5 alpha-A) are found with 5 alpha-A representing the major product. In addition, the cells form diols and 5 alpha-A from [14C]DHT as well as androsterone (A) and DHT from [14C]5 alpha-A; there is a prevalence of diols in the former case, and of A in the latter one. The yields of the different metabolites recovered after 2 h of incubation of the cells with the appropriate labelled substrates are therefore in descending order of magnitude: 5 alpha-A > A > diols > delta 4 > DHT > T. These results are also confirmed by the analysis of the rate of production of the different steroids. Taken together the present results suggest that: (a) qualitatively LNCaP cells possess all the major key enzymes involved in androgen processing; (b) the metabolism of androgens in this cell line resembles quantitatively that found in prostatic cancer tissue; all the metabolic steps which contribute to DHT degradation exceed the ones leading to its accumulation; (c) 5 alpha-reductase shows a significantly higher affinity for delta 4 than for T; (d) LNCaP cells may represent a suitable in vitro model for the study of factors controlling the formation and the degradation of androgens in prostatic carcinoma, thus permitting a better understanding of the metabolic processes involved in prostatic benign or malignant (carcinoma) transformation.
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PMID:Androgen metabolism in the human prostatic cancer cell line LNCaP. 794 55

Products of cis-prenyltransferase activity, the first committed enzyme of the dolichol biosynthetic pathway, have been characterized in Saccharomyces cerevisiae. The evidence based on the results of ion exchange, HPTLC chromatography and acid phosphatase digestion has been presented indicating that the final product of the enzyme action in vitro is free polyprenol and not polyprenol mono- or diphosphate. On the other hand, the results of HPLC analysis confirmed that in vivo yeast accumulate alpha-saturated polyprenols (dolichols). Phosphorylation of endogenous dolichols by cytidine triphosphate (CTP)-dependent kinase is demonstrated. The hypothesis is put forth that in S cerevisiae free polyprenol is the substrate for the alpha-reductase responsible for its conversion to dolichol which in turn is phosphorylated into its active form: dolichyl phosphate.
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PMID:Products of S cerevisiae cis-prenyltransferase activity in vitro. 881 19

Osteoclasts, the bone resorbing cells, are formed from hematopoietic precursors via plasma membrane fusion. To investigate the possibility that cholesterol is involved in cellular fusion events, we examined the effects of the depletion of low density lipoproteins (LDL) and the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on osteoclast-like cell formation. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), osteoclast-like cells, were formed as a result of the coculture of mouse spleen cells with mouse stromal cells TMS-14 in the presence of 1alpha, 25-dihydroxyvitamin D3 (1, 25 VD3). The depletion of LDL suppressed the formation of TRAP-positive MNCs, but the effect was abrogated by the addition of LDL. This inhibitory effect was not observed following the depletion of LDL in the early stages of the culture (day 0-3). The decrease in the number of TRAP-positive MNCs resulting from LDL depletion was accompanied by an increase in the number of TRAP-positive mononuclear cells. Furthermore, the formation of MNCs was also suppressed by the addition of simvastatin, an HMG-CoA reductase inhibitor. The inhibitory effect of simvastatin on the generation of TRAP-positive MNCs was dose and time dependent. However, treatment with simvastatin did not affect the increase in TRAP activities. These results suggest that cholesterol in the membranes of monocytes is involved in osteoclast-like cell formation via cellular membrane fusion events.
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PMID:Involvement of cholesterol in osteoclast-like cell formation via cellular fusion. 970 72

A combination of electrophysiological, pathological, and biochemical studies were performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a hydrophilic inhibitor) were administered by gavage to rabbits. In Group I (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4 weeks), no rabbit showed either condition. In Group III (pravastatin-treated group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit showed muscle necrosis and high serum CK level and two rabbits showed electrical myotonia. The pathological findings were muscle fiber necrosis and degeneration with increased acid phosphatase activity by light microscopy, autophagic vacuoles and mitochondrial swelling, and disruption and hypercontraction of myofibrils by electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36% in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However, mitochondrial enzyme activities of respiratory chain were normal in all groups. These results indicate that myopathy was not induced by a secondary dysfunction of mitochondrial respiration due to low ubiquinone levels.
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PMID:Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study. 977 5

Sexually mature female Wistar rats were given daily intragastric doses of ethinylestradiol (EE) and levonorgestrel (LE) used normally in women: (1) 0.03 mg EE and 0.05 mg LE; (2) 0.04 mg EE and 0.075 mg LE; (3) 0.03 mg EE and 0.125 mg LE. All groups were treated for 6 months in 5-day cycles (four-day treatment with a one-day break), i.e. for 36 sexual cycles. In rat kidneys, the activity of succinic dehydrogenase, NADPH-tetrazolium reductase, Mg(2+)-ATPase and alkaline phosphatase were decreased, while those of lactate dehydrogenase, acid phosphatase and glucose-6-phosphatase were enhanced. We have found a correlation between enzymatic changes and ultrastructural changes in epithelial renal cells. These changes may reflect: (1) inhibited oxidative processes associated with the mitochondrial and microsomal systems of electron transport; (2) a compensatory increase in anaerobic processes; (3) increased glyconeogenesis; (4) inhibited transport processes and increased cellular catabolism. The kidney cortex and medulla did not show any significant morphological changes after 6 months of treatment. The study has shown that EE/LE combinations produce histochemical and ultrastructural changes in the kidney, which are dependent on the doses of gestagens.
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PMID:Effects of ethinylestradiol and levonorgestrel on morphology, ultrastructure and histoenzymatic activity of rat kidney. 980 70

Vitiligo is a common dermatological disorder characterized by the development of complete pigment loss from focal lesions that tends to increase in size over time. The etiology of vitiligo, resulting in the disappearance of functional melanocytes from involved skin, is not clearly understood. As a consequence, no satisfactory therapy has been developed. A subtype of vitiligo, termed 'occupational' or 'contact' vitiligo, is increased in individuals who are exposed to materials containing phenolic derivatives, such as 4-tertiary butylphenol (4-TBP). Phenolic derivatives are structurally similar to tyrosine, the initial substrate of tyrosinase in the biochemical synthesis of melanin. Therefore, it has been proposed that phenolic derivatives compete with tyrosine for hydroxylation by tyrosinase and interfere with the completion of melanin synthesis and/or generate cytotoxic intermediates. Our results demonstrated that 4-TBP competitively inhibited both tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase, i.e., the first two catalytic steps in the biochemical conversion of tyrosine to melanin in cultured human melanocytes. This inhibition occurred at concentrations that did not influence the viability of melanocytes. The tyrosinase activity inhibited by 4-TBP was recovered after removing the treatment. 4-TBP did not affect the function of other enzymes, such as succinate-tetrazolium reductase, acid phosphatase and sulfatase. Since depigmentation occurred without a cytotoxic response after exposure of melanocytes to low concentration of 4-TBP, it is unclear whether the interaction between 4-TBP and tyrosinase leads to the destruction of the melanocytes in 'contact/occupational' vitiligo.
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PMID:Effects of 4-tertiary butylphenol on the tyrosinase activity in human melanocytes. 1045 91

The ability of insulin to influence activities of various protein kinases and protein phosphatases, that are thought to mediate insulin action, are limited in patients with insulin resistance. Because numerous responses to insulin are affected, we undertook studies to determine whether protein tyrosine phosphatases (PTPs) activities are altered in patients with diabetes syndrome. In order to evaluate abnormal PTP activities, we done a comparative study using erythrocytes from normal and diabetic patients. We determined the activity of the cytosolic acid PTP in basal and insulin-dependent states. Mean basal PTP activities, were found to be significantly higher in diabetics than in normal subjects (type 1 diabetics: 0.36 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g hemoglobin (Hb), P < 0.001; type 2 diabetics: 0.35 +/- 0.01 vs 0.28 +/- 0.01 mmol p-nitrophenolate/h per g Hb, P < 0.001). Insulin, at concentrations above physiological levels (1 mIU/ml), inhibited the PTP activities in erythrocytes from normal subjects (-15 +/- 4.1%, P < 0.01). Insulin could also modulate glycolysis, probably as a consequence of receptor tyrosine kinase activation, inducing phosphorylation of protein band 3 and hence the release of glycolytic enzymes. We have previously reported that a reductase enzyme in human erythrocytes is dependent on glycolysis being significantly activated (+28 +/- 3.1%, P < 0.001) by high insulin levels (1 mIU/ml). Mean basal reductase activities were found to be significantly lower in diabetics than in normal subjects (type 1 diabetics: 0.77 +/- 0.03 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001; type 2 diabetics: 0.77 +/- 0.04 vs 0.97 +/- 0.02 mmol ferrocyanide/20 min per l cells, P < 0.001), indicating altered erythrocyte metabolism in the diabetic patients. High glucose levels were used to mimic hyperglycemia condition, using erythrocytes from normal subjects. At 30 mM glucose, erythrocytic phosphatase activity was stimulated (+32 +/- 4.2%, P < 0.0001), although no effect was observed on the reductase enzyme at the same glucose levels. Results indicated that diabetic disorders appear to be associated with quantitative alterations of erythrocyte acid phosphatase activity and other enzymes that depend on the glycolytic rate (reductase). The overall data suggest that erythrocyte acid phosphatase may have a role in the modulation of glycolytic rates through the control of insulin receptor phosphorylation.
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PMID:Insulin and high glucose modulation of phosphatase and reductase enzymes in the human erythrocytes: a comparative analysis in normal and diabetic states. 1074 68

The histochemical and enzyme cytochemical effects of Toxaphene were investigated using isolated hepatocytes in suspension culture from laboratory-bred juvenile, female yellowtail flounder (Pleuronectes ferrugineus). Hepatocytes were kept in suspension culture for 4 days and exposed for 3 days to a control medium, to a medium with hexane (the solvent of Toxaphene), or to a medium with Toxaphene in two different concentrations (1 and 10 mocrog/ml). Subsequently, the cultivated cells were examined histochemically (Sudan black B, oil red O, Schmorl's reaction) and enzyme cytochemically (acid phosphatase, NADPH-ferrohemoprotein reductase). Toxaphene decreased the viability of the isolated cells significantly, as compared to the control suspensions. Toxaphene also increased the storage of total and neutral lipids (as demonstrated by Sudan black B and oil red O, respectively) in a dose-dependent manner. In addition, Toxaphene increased the enzymatic activity of acid phosphatase, and increased the storage of lipofuscin pigment (as demonstrated by the Schmorl's reaction) within the hepatocytes, suggesting an increase in the number and/or size of the lysosomes. Hexane did not have a significant toxic effect on the isolated hepatocytes. It is concluded that Toxaphene is potentially toxic to fish in a marine environment and that this in vitro system may provide a model for assessing the direct effect of various toxicants on fish hepatocytes.
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PMID:Effect of toxaphene on isolated hepatocytes of the yellowtail flounder, Pleuronectes ferrugineus storer. 1090 26

Biliverdin reductase (BVR) reduces heme oxygenase (HO) activity product, biliverdin, to bilirubin. BVR is unique in having dual pH/dual cofactor requirements. Using Escherichia coli-expressed human BVR and COS cells, we show that BVR is autophosphorylated and that phosphorylation is required for its activity. An "in blot" autophosphorylation assay showed that BVR is a renaturable phosphoprotein. Controls for the experiments were HO-1 and HO-2; both are phosphoproteins but are not autophosphorylated. Autophosphorylation was pH-dependent, with activity at pH 8.7 being most prominent. In addition, 2'(3')-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate fluorescence titration of BVR gave a lower K(d) at pH 8.7 than at pH 7.4 (15.5 versus 28.0 micrometer). Mn(2+) was required for binding of the ATP analogue and for autophosphorylation; the autokinase activity was lost when treated at 60 degrees C for 10 min. The loss of transferred phosphates by alkaline treatment suggested that BVR is a serine/threonine kinase. Potato acid phosphatase treatment reversibly inactivated the enzyme. The enzyme was also inactivated by treatment with the serine/threonine phosphatase, protein phosphatase 2A; okadaic acid attenuated the inhibition. Titration of protein phosphatase 2A-released phosphates indicated a 1:6 molar ratio of BVR to phosphate. The BVR immunoprecipitated from COS cell lysates was a phosphoprotein, and its activity and phosphorylation levels increased in response to H(2)O(2). The results define a previously unknown mechanism for regulation of BVR activity and are discussed in the context of their relevance to heme metabolism.
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PMID:Human biliverdin reductase is autophosphorylated, and phosphorylation is required for bilirubin formation. 1127 40


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