共查询到20条相似文献,搜索用时 15 毫秒
1.
Raad I Terreux R Richomme P Matera EL Dumontet C Raynaud J Guilet D 《Bioorganic & medicinal chemistry》2006,14(20):6979-6987
A set of 32 natural and synthetic coumarins were tested in order to evaluate their activity on human leukemic cells (K562/R7) overexpressing P-glycoprotein (P-gp). Their ability to reduce the P-gp-mediated drug efflux of daunorubicin out of cells was evaluated at 10 microM. Four natural compounds, previously isolated from Calophyllum dispar (Clusiaceae) and substituted by a common alpha-(hydroxyisopropyl)dihydrofuran moiety, exhibited a significant inhibitory effect on P-gp when compared to the positive control cyclosporin A. A 3D-quantitative structure-activity relationship (3D-QSAR) analysis of the coumarins was performed using the biological results obtained by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of P-gp. Results showed a favorable electrostatic and steric volume, like the alpha-(hydroxyisopropyl)dihydrofuran moiety, beside C(5)-C(6) or C(7)-C(8) positions. In addition, the analysis revealed an important hydrophobic, neutral charge group, like phenyl, in position C(4) on the coumarinic ring. 相似文献
2.
Halothane concentration (g/g wet weight) was measured in rat brain and liver following exposure to various concentrations of halothane in air. Because of the difficulty of determining the amount of a volatile compound in brain, we analyzed tissue fixed by two different methods. The apparent concentration of halothane in brain was higher following direct decapitation into liquid nitrogen, than after decapitation, removal of fresh tissue, and then freezing. However, the relative effects of altering the inspired concentration were essentially the same in each case. Thus, absolute quantitative accuracy remains a point for discussion; however, we can reach several conclusions regarding the relative accumulation of halothane in brain tissue following various conditions of exposure. Resultant tissue concentrations of halothane were not linearly related to ambient concentrations. Above an inspired concentration of 1.0%, an increase to 1.5% inspired concentration caused little further increase in the halothane concentration in brain, although the liver concentration increased in proportion to the dose increase. Below an inspired concentration of 0.5%, tissue concentrations were less than expected, probably as a result of metabolic degradation occurring at a rate that becomes more noticeable at lower inspired concentrations. Body size was shown to be an important variable affecting the time required for each tissue to reach equilibrium at a given inspired concentration. These data indicate that tissue concentrations at low exposure levels may be less than proportional to dose and that concentrations in small laboratory animals may be expected to exceed values in humans under equivalent conditions of exposure. 相似文献
3.
4.
Biosynthesis of serum albumin in rat liver. Isolation and probable structure of ''proalbumin'' from rat liver. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《The Biochemical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
1. Two methods are described for the preparation of 'proalbumin' in good yields from rat liver. 2. One of the methods does not depend on the use of specific antisera. 3. The product from both methods is identical as judged by electrophoresis on polyacrylamide gel, isoelectric focusing on pH gradients, ion-exchange chromatography and quantitative immunoelectrophoresis. The protein also appears to be radiochemically pure by these criteria. 4. The protein is free from serum albumin as judged by isoelectric focusing and co-chromatography on ion-exchange columns. It is judged to be free from other proteins by these same criteria and by specific precipitation with antibody. 5. It is converted into serum albumin by limited tryptic hydrolysis. The albumin so produced has the same N-terminal (glutamic acid) and C-terminal (alanine) amino acids as reported for rat serum albumin. 6. A hexapeptide is liberated from the N-terminal end of 'proalbumin' simultaneously. It contains three arginine, one phenylalanine, one valine and one glycine residues. 相似文献
5.
The relationship between milk accumulation and enzyme activities in the involuting rat mammary gland 总被引:3,自引:0,他引:3
E A Jones 《Biochimica et biophysica acta》1969,177(1):158-160
6.
The amount of total monovalent cations in leaves of Sorghum bicolor , L. Moench, RS 610, which were exposed to salinity stress, was a function of both the osmotic potential and the concentration of K+ of growth media. The plants have a Na+ exclusion mechanism that keeps the level of Na+ in leaves low. Thus, most of the osmotic adjustment in leaves was due to K+ . Proline did not start to accumulate in leaves until the concentration of total monovalent cations in leaves reached a threshold of approximately 200 μmol/g fresh weight. Above this threshold, the contents of prolioe and monovalent cations in leaves increased with increasing salinity of the medium. The ratio of proline to monovalent cation was 5% of that amount of monovalent cation in excess of the threshold concentration. Therefore, if the cations are located in the vacuoles and proline accumulates in the cytoplasm, then the amount of accumulated proline is sufficient to act as a balancing osmoticum across the tonoplast. Very little proline accumulated in roots because this tissue contained much less total monovalent cations than leaves from the same salt-stressed plants. The same threshold of 200 μmol/g fresh weight of total monovalent cations was required in roots as in leaves to initiate proline accumulation. 相似文献
7.
PETER S. COOPER 《Biomarkers》2013,18(1):48-58
P-glycoproteins (Pgps) are involved in efflux of xenobiotics from drug-resistant cell lines and tumours, and in excretion of toxicants from normal tissues. Recently, investigators have proposed that Pgp activity contributes to resistance or tolerance of certain aquatic species to pollutants. In the present study using immunoblot and immunohistochemical techniques, we found elevation of Pgp in liver and liver tumours of creosote-resistant mummichog from a contaminated site in the Elizabeth River, Virginia. Immunoblots of mummichog liver extracts showed an immunoreactive band at 170 kDa and indicated two- to three-fold elevation of Pgp in livers of resistant fish relative to those from a reference site. Laboratory exposures of reference site fish to a model PAH (3-methylcholanthrene), however, produced no increase in liver Pgp levels as measured by immunoblot. Normal mummichog liver sections showed specific immunohistochemical staining for Pgp on the canalicular surface of hepatocytes. In the majority of hepatic neoplasms we observed a high level of over-expression and altered patterns of Pgp expression. However we did not observe Pgp over-expression in early proliferative lesions. Elevation of Pgp in livers and liver tumoursof these resistant mummichog may contribute to their survival in a heavily contaminated environment. 相似文献
8.
Peter S. Cooper 《Biomarkers》1999,4(1):48-58
P-glycoproteins (Pgps) are involved in efflux of xenobiotics from drug-resistant cell lines and tumours, and in excretion of toxicants from normal tissues. Recently, investigators have proposed that Pgp activity contributes to resistance or tolerance of certain aquatic species to pollutants. In the present study using immunoblot and immunohistochemical techniques, we found elevation of Pgp in liver and liver tumours of creosote-resistant mummichog from a contaminated site in the Elizabeth River, Virginia. Immunoblots of mummichog liver extracts showed an immunoreactive band at 170 kDa and indicated two- to three-fold elevation of Pgp in livers of resistant fish relative to those from a reference site. Laboratory exposures of reference site fish to a model PAH (3-methylcholanthrene), however, produced no increase in liver Pgp levels as measured by immunoblot. Normal mummichog liver sections showed specific immunohistochemical staining for Pgp on the canalicular surface of hepatocytes. In the majority of hepatic neoplasms we observed a high level of over-expression and altered patterns of Pgp expression. However we did not observe Pgp over-expression in early proliferative lesions. Elevation of Pgp in livers and liver tumoursof these resistant mummichog may contribute to their survival in a heavily contaminated environment. 相似文献
9.
Y Yamada Y Seino J Takeda H Fukumoto H Yano N Inagaki Y Fukuda S Seino H Imura 《Biochemical and biophysical research communications》1990,168(3):1274-1279
Gene expression of liver facilitated glucose transporter was rapidly induced during the liver regenerating process in rats. It reached maximum of 2.7 times at 8 hr of the regenerating course and returned to normal by 48 hr. The protein synthesis inhibitor, cycloheximide, did not interfere with the increased gene expression of liver facilitated glucose transporter. By contrast, erythrocyte/brain-type glucose transporter mRNA could not be detected in the livers of partially hepatectomized rats and sham-operated rats. The plasma glucose levels were transiently increased within 2 hr of the regenerative course and then decreased to a nadir at 4 hr. These results suggest that the increased gene expression of liver facilitated glucose transporter contributes to the decrease in plasma glucose levels. 相似文献
10.
The relationship between palmitoyl-coenzyme A synthetase activity and esterification of sn-glycerol 3-phosphate in rat liver mitochondria 总被引:24,自引:24,他引:0
1. The specific activities for palmitoyl-CoA synthetase and for sn-glycerol 3-phosphate esterification, with palmitoyl-CoA generated either by the endogenous synthetase or from palmitoyl-(−)-carnitine, CoA and excess of carnitine palmitoyltransferase, were measured with rat liver mitochondria. 2. The mean specific activity of palmitoyl-CoA synthetase was approximately five- and seven-fold the rates of sn-glycerol 3-phosphate esterification from palmitate and palmitoyl-(−)-carnitine respectively. No significant correlation was found in different rats between the activities of palmitoyl-CoA synthetase and sn-glycerol 3-phosphate esterification from either acyl precursor. However, there was a significant correlation (r=0.83, P<0.001) between the rates of glycerolipid synthesis from palmitate and palmitoyl-(−)-carnitine. 3. The mean molar composition of the glycerolipid synthesized from palmitate was 58% lysophosphatidate, 31% phosphatidate and 11% neutral lipid. With palmitoyl-(−)-carnitine the equivalent values were 70, 23 and 7%, which were significantly different. 4. When palmitoyl-CoA synthetase had been inactivated by 60–70% after preincubation of mitochondria at 37°C, it became rate-limiting in glycerolipid biosynthesis. Additions of 1–5mm-ATP prevented inactivation of palmitoyl-CoA synthetase. 5. Preincubation also inhibited the oxidation of palmitate, palmitoyl-CoA, palmitoyl-(−)-carnitine and malate plus glutamate. These inhibitions could not be prevented by addition of ATP. 6. Diversion of palmitoyl-CoA to form palmitoyl-(−)-carnitine did not inhibit sn-glycerol 3-phosphate esterification. 7. The palmitoyl-CoA pool synthesized by the palmitoyl-CoA synthetase was augmented by adding partially purified synthetase or carnitine palmitoyltransferase and palmitoyl-(−)-carnitine. No stimulation of palmitate incorporation into glycerolipids occurred. 8. At low concentrations of Mg2+, palmitate, ATP and CoA the velocity with palmitoyl-CoA synthetase decreased more than that of glycerolipid synthesis from palmitate. 9. It is concluded that in the presence of optimum substrate concentrations the activity of sn-glycerol 3-phosphate acyltransferase and not of palmitoyl-CoA synthetase is rate-limiting in the synthesis of phosphatidate and lysophosphatidate in isolated rat liver mitochondria. 相似文献
11.
12.
Summary Two isoforms of facilitative glucose transporters (GLUT), namely the erythroid/brain-type GLUT 1 and the liver-type GLUT 2, were demonstrated in native cryostat sections of normal rat liver and brain by immunofluorescence and a very sensitive immunoalkaline phosphatase reaction. Fixation with 0.1% alcoholic periodic acid resulted in an excellent localization of GLUT 2 in liver and GLUT 1 in brain. GLUT 1 in liver, however, could successfully be demonstrated after fixation with 1% alcoholic formaldehyde. GLUT 2 occurred in all hepatocytes as a basolateral membrane protein with a gradient of high expression in the periportal area and a lower one in the perivenous part. The first layer of hepatocytes adjacent to the hepatic vein coexpressed GLUT 1. In addition, GLUT 1 could be detected in the smooth muscle layer of the portal vein and in the apical and lateral plasma membrane of the bile duct epithelium. In brain, GLUT 1 showed a high expression in the microvessels, the ependym and in the basal plasma membrane of choroid plexus epithelial cells. The blood capillaries associated with the choroidal epithelium were, however, negative for GLUT 1. The importance of the new findings in this study for the physiological role of the respective facilitative glucose transport proteins is discussed. 相似文献
13.
S Shinozawa Y Gomita Y Araki 《Physiological chemistry and physics and medical NMR》1991,23(2):101-106
The effects of Aclarubicin (aclacinomycin A; ACM) and Doxorubicin (adriamycin; ADM) on oxidative phosphorylation in rat liver mitochondria were studied in vitro. The state 3 oxygen uptake of mitochondria was reduced by only 2% by 20 microM of ADM, while the same concentration of ACM caused a 67% reduction. When 20 microM of ADM acted on state 4a oxygen uptake of mitochondria, only a slight decrease in state 3, state 4b, dinitrophenol-stimulated respiration and the respiratory control index was observed. In contrast 20 microM of ACM caused significant inhibition of all the above factors when compared with the controls. It was concluded that ACM has strong inhibitory action on the mitochondrial electron transfer system in vitro, and that one can expect functional failure of mitochondria to occur clinically during adverse response to the administration of this drug. 相似文献
14.
Glucosylceramide, radiolabelled on the glucose residue, was administered to rats and the radioactive gangliosides formed at different time points were chemically characterized. They were identified as GM3, GM1, GD1a and GD1b, each one carrying only radioactive glucose. The time course of each individual ganglioside showed that the simpler gangliosides were formed earlier but were consumed earlier than the more complex ones, resulting in radioactivity patterns that were different at each time point. Only 30 h after injection did it resemble that of endogenous rat liver gangliosides. These results indicate that an extensive precursor-product relationship actually exists in the course of ganglioside biosynthesis. 相似文献
15.
Similarities between rat liver mitochondrial and cytosolic glutathione reductases and their apoenzyme accumulation in riboflavin deficiency 总被引:1,自引:0,他引:1
Glutathione reductase has been purified 5,500-fold from rat liver mitochondrial matrix in a yield of 30%. The mitochondrial enzyme was immunochemically indistinguishable from that of the cytosol and the subunit molecular weight was apparently similar to that of the cytosolic enzyme, that is, 50,000 daltons. The optimum pH and kinetic properties investigated were not significantly different from those of the cytosolic enzyme. When rats were fed a riboflavin-deficient diet, the enzyme activity in the mitochondria decreased to a greater extent than that in the cytosol, and greater accumulation of apo-enzyme in the former than that in the latter was confirmed by the amount of immunoprecipitable protein, activation by FAD addition in vitro, and the enzyme activity recovery after injection of riboflavin, into riboflavin-deficient rats. 相似文献
16.
17.
18.
Although anthracycline antibiotics daunorubicin (DR), doxorubicin (DX), and epirubicin (ER) possess minor differences in their
chemical structures, large differences are noted in their clinical use, as well as in cellular and plasma pharmacokinetic
parameters in vivo. Immunocytochemistry for DR, DX, or ER was developed using an anti-DR monoclonal antibody (ADM-1-11), which
has been demonstrated to react equally well with each of the three drugs, and therefore it was used for comparing their accumulation
in several rat tissue cells after a single i.v. injection of each drug. In the kidney, immunoreactivity for each drug was
distributed in essentially the same pattern and in the same strength 2 h after injection, but quite differently distributed
in kidney cells thereafter, so that at 120-h post-injection significant amounts of DX and ER remained, but DR had almost completely
vanished. Similar patterns of accumulation were observed in cells of other tissues including the pancreas, hair follicle,
and stomach, with the exception of the intestine in which none of the three drugs remained after 120 h. These results appear
to be supported by previous pharmacokinetic studies on the anthracyclines. The mechanism for such differences among the three
drugs remains obscure, but the hydroxyl group at C-14 of DX and ER molecule might be related to the strong propensity of DX
and ER to accumulate in tissue cells. The present results should contribute to the understanding of the mechanisms of the
differences in the pharmacokinetics, as well as the possibly in anti-tumor activities of the anthracyclines. 相似文献
19.
20.
Tamoxifen can induce hepatic steatosis in women. In this study, we wanted to elucidate the mechanism behind the tamoxifen-induced accumulation of triacylglycerol in liver in female rats, and we hoped to prevent this development by combination treatment with the modified fatty acid tetradecylthioacetic acid (TTA). The increased hepatic triacylglycerol level after tamoxifen treatment was accompanied by decreased acetyl-coenzyme A carboxylase (ACC) and FAS activities, increased glycerol-3-phosphate acyltransferase (GPAT) activity, and a tendency to increased diacylglycerol acyltransferase (DGAT) activity. The activities and mRNA levels of enzymes involved in beta-oxidation, ketogenesis, and uptake of lipids from liver were unaffected by tamoxifen, whereas the uptake of lipoproteins was unchanged and the uptake of fatty acids was decreased. Combination treatment with tamoxifen and TTA (Tam+TTA) normalized the hepatic triacylglycerol level and increased the activities of ACC, FAS, GPAT, and DGAT compared with tamoxifen-treated rats. The activities and mRNA levels of enzymes involved in beta-oxidation, ketogenesis, and uptake of lipids were increased after Tam+TTA treatment. In conclusion, tamoxifen increased the hepatic triacylglycerol level, probably as a result of increased triacylglycerol biosynthesis combined with unchanged beta-oxidation. The tamoxifen-induced accumulation of triacylglycerol was prevented by cotreatment with TTA, through mechanisms of increased mitochondrial and peroxisomal beta-oxidation. 相似文献