Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides with Fe2+ and citrate results in rapid O2-dependent inactivation of the enzyme. Maximal rate of inactivation occurred at equimolar concentrations of Fe2+ and citrate. Loss of enzyme activity appears to be the result of selective oxidative modification, as evidenced by a corresponding increase in protein carbonyl content. Partially inactivated enzyme remained predominantly in the dimeric form with no change in the apparent affinity of the remaining active subunits for substrate. Modified Glu-6-PDH was, however, more susceptible to heat denaturation. Our results suggest that the Fe(2+)-citrate complex binds to the glucose 6-phosphate binding site and then undergoes reaction with H2O2 formed in solution leading to the oxidative modification of amino acids essential for enzyme activity.
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PMID:Oxidative modification of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides by an iron(II)-citrate complex. 846 Sep 48

We have previously shown that incubation of the model protein glucose-6-phosphate dehydrogenase (Glu-6-PDH) from the bacterium Leuconostoc mesenteroides with 4-hydroxy-2-nonenal (HNE), a major product of lipid peroxidation, results in the formation of cross-linked protein. HNE-modified protein is resistant to proteolytic degradation and acts as an inhibitor of the multicatalytic proteinase. It was therefore important to establish the chemistry of the cross-linking reaction. The formation of cross-linked Glu-6-PDH is associated with the nearly exclusive loss of lysine residues. For this reason the reaction of N-acetyllysine with HNE has been investigated. The epsilon-amino group of lysine reacts with the double bond (C3) and the carbonyl (C1) functions of HNE via Michael addition and Schiff base formation resulting in the production of a 2:1 amino acid-HNE cross-link. Chromatographic detection of this adduct in the acid hydrolysate of HNE-treated Glu-6-PDH reveals that this chemistry is responsible for the formation of cross-linked protein. Antibody to the reduced form of the 2:1 lysine-HNE adduct was prepared. The antibody was used to demonstrate that exposure of isolated liver mitochondria to oxidative stress led to the formation of intra- and intermolecular protein-HNE cross-links. The results of the present study indicate that modifications to protein by lipid peroxidation products may be physiologically relevant and could contribute to the disease- and age-related buildup of damaged protein.
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PMID:Chemical characterization of a protein-4-hydroxy-2-nonenal cross-link: immunochemical detection in mitochondria exposed to oxidative stress. 863 25

In the liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4), the change in lipid peroxide (LPO) level with the development of damage over a 24 hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se-independent glutathione peroxidase (non-Se-GSH-px) with the development of damage during the same period. An apparent liver injury was observed 0.5 hr after CCl4 treatment and the injury progressed rapidly later than 8 hr, judging from the activities of serum transaminases, marker enzymes of liver cell damage. Hepatic LPO level slightly increased once during the first 4 hr after CCl4 treatment and a marked increase in the level occurred later than 12 h, while serum LPO level increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4 hr after CCl4 treatment and the decreased level recovered slowly thereafter, although the recovered level did not reach the control level. Hepatic GSSG level rapidly increased once during the first 1 hr after CCl4 treatment and an increase in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity increased during the first 2 hr after CCl4 treatment and later than 8 h, while hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased during the first 2 hr after CCl4 treatment but the decrease activity returned up to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter. These results indicate that although hepatic lipid peroxidation is enhanced at early and progressed stages of liver injury in mice intoxicated once with CCl4, endogenous GSH through hepatic glutathione redox cycle can respond well to enhanced hepatic lipid peroxidation at an early stage of liver injury but not enough to enhanced hepatic lipid peroxidation at a progressed stage of liver injury.
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PMID:Response of endogenous reduced glutathione through hepatic glutathione redox cycle to enhancement of hepatic lipid peroxidation with the development of acute liver injury in mice intoxicated with carbon tetrachloride. 888 91

Alterations in uterine nuclear and cytosolic estradiol (ER) and progesterone (PR) receptor concentration, activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH), surface and transmission electron microscopy and histology in relation to the time of secretion of nidatory estrogen and the onset of endometrial sensitivity in the rat were investigated. A significant increase in plasma estradiol (E2) concentration in control rats was observed at 22.00 h on day 4 post-coitum, whereas progesterone (P) concentration increased at 17.00 h on day 4 and was maintained until 17.00 h on day 5. The period of high endometrial sensitivity (10.00 h on day 5) was characterized by elevated uterine cytosolic ER and nuclear and cytosolic PR concentration and POD activity, low columnar luminal epithelium with undulating surface and intercellular membranes, covered with short microvilli and pinopods, and containing numerous electron-transparent apical vesicles, mitochondria, polyribosomes, rough (RER) and smooth (SER) endoplasmic reticulum, well developed Golgi, few lysosomes and lipid droplets and loose edematous antimesometrial stroma. Inhibition in endometrial sensitivity by post-coital centchroman was associated with a marked depletion in uterine cytosolic ER and an increase in nuclear ER concentration, a decrease in POD and G-6-PDH activities, compact fibroblastic stroma, an increase in luminal epithelial cell height with decreased RER, SER, polyribosomes, Golgi, straightening of intercellular membranes, reduced surface undulations and absence of pinopods. Electron-transparent vesicles appeared flattened and clumped in the apical portion of cells, tight junctions were more prominent and lipid droplets were translucent. Nuclear and cytosolic PR and the pattern of secretion or plasma E2 and P remained unaffected. CAT, SOD and LDH activities, although high throughout pre-implantation, did not vary in relation to the secretion of nidatory estrogen, endometrial sensitivity or centchroman treatment.
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PMID:Uterine estradiol and progesterone receptor concentration, activities of certain antioxidant enzymes and dehydrogenases and histoarchitecture in relation to time of secretion of nidatory estrogen and high endometrial sensitivity in rat. 901 Mar 37

Oxidative modification of glucose-6-phosphate dehydrogenase (Glu-6-PDH), as observed for other proteins, increases the susceptibility of the protein to degradation by the multicatalytic proteinase/proteasome (MCP). Oxidized Glu-6-PDH is, however, more prone to cross-linking reactions by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE), processes which render the protein resistant to proteolysis. In addition, HNE cross-linked protein inhibits the degradation of oxidatively modified glutamine synthetase by the MCP. In contrast to oxidized Glu-6-PDH, which inhibits the proteolysis of GS in a competitive manner, HNE cross-linked protein acts as a noncompetitive inhibitor. As judged by binding of the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid, a common structural feature of both macromolecular substrates and inhibitors of the MCP is an increased accessibility of hydrophobic regions on the protein.
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PMID:Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein. 909 17

Influence of a new sorbent based on the AU-L lignin on the hepatic enzyme spectrum has been investigated in rats with experimental toxic hepatitis. The intact animals were in control group. There was a shift in lactate dehydrogenase (LDH) isoenzymic spectrum to the LDH5 side, glucose-6-phosphate dehydrogenase (G-6-PDH) activity increased to 144.7% against the control. Aspartate aminotransferase (AsT) activity reduced 2 times and alanine aminotransferase (ALT) activity enhanced 1.3 times, LDH2 activity increased 2.8 times in the liver of rats with toxic hepatitis which received sorbent for 7 days versus the untreated animals. The LDH4 and LDH5 fractions activity lowered to the level of the intact animals. G-6-PDH activity continued to increase, aminotransferase activity reduced up to the level less than control. The aerobic shifts in the LDH isoenzymic spectrum in which LDH4 and LDH5 fractions' activity completely returned to the control level evidence for glycolysis conversion to the aerobic type that apparently was promoted by positive effects of enterosorbent.
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PMID:[Effect of enterosorption effects on hepatic enzyme spectrum in experimental toxic hepatitis]. 947 96

A new mycotoxin product (NMP) was isolated from the culture of mutated wild strain of P. nigricans which is less toxic and has sterol derivative. NMP (LD50 > 1 g/kg) showed antimicrobial and antineoplastic activities and does not affect the hematological parameters like RBC count and hemoglobin. It maintained normal blood glucose level by increasing the enzyme activity of glucose-6-phosphate dehydrogenase (EC-1.1.1.49; G-6-PDH) by 30%. It also maintained the normal ion balance in the blood of mice. NMP decreased Km value of glucose-6-phosphate dehydrogenase and thus increased substrate affinity of the enzyme. Reduction of toxicity of NMP has been well explained by higher activity of G-6-PDH which is highly specific for production of NADPH.
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PMID:Effect of mycotoxins isolated from Penicillium nigricans on glucose-6-phosphate dehydrogenase. 956 55

The lowering of activity of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (alpha GPDH), glucose-6-phosphate dehydrogenase (G-6-PDH), the raising of activity of lactate dehydrogenase (LDH) was noted in neutrophil granulocytes in an acute experimental pancreatitis. The prophylaxis of SDH, alpha GPDH, G-6-PDH activity lowering and LDH activity raising was promoted by trental and thiotriazoline injection.
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PMID:[Effects of trental and thiotriazoline on neutrophil dehydrogenase activity in acute experimental pancreatitis]. 967 Jul 35

The contribution of gluconeogenesis to hyperglycemia in non-obese diabetic (NOD) mice has been investigated using oral vanadate administration. Vanadate compounds have been shown to mimic many actions of insulin; however, the exact mechanism is poorly understood. The aims of the present study were (1) to elucidate vanadate's action in vivo, and to assess the possibility that its glucose-reducing effect is dependent on the presence of a minimal concentration of insulin; and (2) to evaluate the effects of vanadate administration on the key hepatic gluconeogenesis enzymes, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), as well as glucose-6-phosphate dehydrogenase (G-6-PDH). Vanadate caused a significant reduction in blood glucose but failed to normalize it, despite effective serum vanadate concentrations (26.2 +/- 1.6 micromol/L). Two weeks after initiation of treatment, blood glucose levels were 26.0 +/- 1.8, 21.7 +/- 3.0, 16.0 +/- 1.6, and 14.3 +/- 2.3 mmol/L in the control (C), insulin (I), vanadate (V), and combined vanadate and insulin (V + I) groups, respectively (P < .001). G-6-Pase activity was significantly reduced by vanadate (622 +/- 134 v365 +/- 83 nmol/min/mg protein in C vV, P < .05). PEPCK activity was also significantly reduced (844 +/- 370, 623 +/- 36, 337 +/- 43, and 317 +/- 75 nmol/min/mg in the C, I, V, and V + I groups, respectively, P < .001). No significant differences in the hepatic glycogen stores and G-6-PDH activity were noted between treatment groups. Our study suggests that the inhibition of hepatic G-6-Pase and PEPCK activity by vanadate plays an important role in reducing blood glucose levels in NOD mice.
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PMID:Gluconeogenesis in non-obese diabetic (NOD) mice: in vivo effects of vandadate treatment on hepatic glucose-6-phoshatase and phosphoenolpyruvate carboxykinase. 1072 8

Many of the discoveries of multidrug resistance (MDR) have resulted from studies using drug-resistant cultured tumor cell lines as experimental models. To date, there has been no report on the detailed characterization of such a cell line from renal cell carcinoma (RCC). By long-term exposure of an established RCC (RCC8701) to increasing concentrations of adriamycin, we established a series of subcultures that were considerably more resistant to the cytotoxic effect of this drug. Biological morphology and cell cycles were analyzed by morphometry and flow cytometry. The chemoresistance index of cells were measured by methyl tetrazolium assay. For evaluation of the expression of MDR-related protein (MRP), mdr-1, glutathione transferase (GST-pi), and topoisomerase II mRNAs, the reverse transcription-polymerase chain reaction was used. Membranous expression of mdr-1-related p-glycoprotein was analyzed by immunofluorescence cytometry. The intracellular content of both glutathione (GSH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were measured using a capillary electrophoresis method. Compared with parent cells, the resistant sublines had a slower growth rate and lower confluent density. They were smaller and mixed with giant cells in different sizes and with different numbers of nucleoli. Flow cytometric analyses showed that resistant cells had a greater percentage of cells in the G2/M phase. The resistant cells, RCC8701/ADR800, were 122 times more resistant to adriamycin and 238 times more resistant to epirubicin than the parent cells. The resistant cells also demonstrated cross-resistance to cisplatin and 5-fluorouracil. In addition to MRP, the contents of mRNA coding for mdr-1, GST-pi, and topoisomerase II in the MDR sublines were higher than in the native cell line. A higher content of cytoplasmic GSH and G-6-PDH were found in the resistant cells; however, the expression of the MDR-related membranous glycoprotein, p-glycoprotein, was not raised. The adriamycin-induced MDR sublines may be used as an experimental system for the search of a means to overcome drug resistance and elucidate possible mechanisms of acquired MDR involved in human renal cancer.
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PMID:Establishment and characterization of renal cell carcinoma cell lines with multidrug resistance. 1085 Jun 29


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