摘要:

AbstractA kinetic analysis of cytochrome P450‐mediated desulfuration (activation) or dearylation (detoxication) showed that rat hepatic microsomes have a greater capacity to detoxify and a lower capacity to activate chlorpyrifos compared to parathion. Kinetic curves for the desulfuration of both parathion and chlorpyrifos were biphasic;K m apps of 0.23 and 71.3 μM were calculated for parathion, and 1.64 and 50.4 μM for chlorpyrifos. While phenobarbital (PB) exposure seemed to generally lower theKmapps for desulfuration except for the lowKmactivity on chlorpyrifos, the results were not statistically significant. While the lowKmactivity contributed 44 and 60% of the control Vmaxfor parathion and chlorpyrifos, respectively, it contributed 50 and 17% in PB‐treated rats. These studies have indicated the presence of a lowKmactivity capable of functioning at very low substrate concentrations. A single dearylationK m appwas calculated, 56.0 and 9.8 μM for parathion and chlorpyrifos, respectively. Phenobarbital exposure seemed to raise theK m apps of dearylation; however, again, the results were not statistically significant. While numerous biochemical factors contribute to the overall toxicity levels of phosphorothionate insecticides, thein vitroefficiencies of hepatic microsomal desulfuration and dearylation of parathion and chlorpyrifos correspond to the acu

ISSN:0887-2082    

DOI:10.1002/jbt.2570100202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe influence of thyroid hormone administration on liver glutathione (GSH) extraction in the isolated perfused liver was studied in fed rats for a period of 1–7 days following a single dose of 0.1 mg 3,5,3′‐triiodothyronine (T3)/kg. T3treatment led to an early and transient calorigenic response, as well as an enhancement in liver GSH removal, reaching a maximal effect at 2 days after hormone administration, which was normalized in the 3‐ to 7‐day period studied. Addition of the γ‐glutamyltransferase (γ‐GT) inhibitor DL‐serineborate (4 mM) to the perfusate abolished the increase in the hepatic removal of GSH elicited by T3, and enhanced the sinusoidal concentration of GSH, studied at 2 days after hormone administration. These data support the role of hepatic basolateral γ‐GT ectoactivity in the depletion of portally added and liver‐derived GSH as an adaptive response to recover GSH levels after reduction by T3‐

ISSN:0887-2082    

DOI:10.1002/jbt.2570100203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractA biphasic increase of hemolymph glucose levels was observed following injection to bees of cupric gluconate or sulfate, both potent agents for the control ofVarroa jacobsoni, a parasitic mite of hives. The simultaneous injection to bees of 0.3 μM BAYg5421 (an inhibitor of α‐glucosidases) quenched the response, suggesting a direct effect of 2 nmol/bee cupric ions on trehaloses' activity. One nanomol of injected cupric gluconate increased the trehalose (Tre) activity by 233% in crude hemolymph extracts at 1 mM trehalose concentration, and exhibited biphasic dose‐related effects with a maximum 15% increase at 0.5 mM cupric ion and a stabilized 20% inhibition from 4 mM, regardless of the anionic moiety. Upon partial purification of the enzyme complex, two fractions (FI = 75% and FII = 25% of total activity) were isolated that exhibited, respectively, less and more marked positive cooperativity than crude extract. Form I showed almost no susceptibility to either cupric derivatives, which indicated form II as the most likely target, with 68% and 72% increases with 0.25 mM cupric sulfate and 0.5 mM cupric gluconate, in presence of 16 mM treh

ISSN:0887-2082    

DOI:10.1002/jbt.2570100204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe peroxisome proliferators perfluorooctanoic acid (PFOA; 0.02% w/w), perfluorodecanoic acid (PFDA; 0.02%, w/w), nafenopin (0.125%, w/w), clofibrate (0.5%, w/w), and acetylsalicylic acid (ASA; 1%, w/w) were administered to male C57 BL/6 mice in their diet for two weeks. Parameters for Fe3+ADP, NADPH or ascorbic acid‐initiated lipid peroxidation in vitro were measured. Approximately a twofold increase in susceptibility to lipid peroxidation was obtained for all the peroxisome proliferators tested. Cotreatment of mice with the peroxisome proliferator ASA (1%, w/w) and a catalase inhibitor, 3‐amino‐1,2,4‐triazole (AT; 0.4%, w/w) for 7 days resulted in little inhibition of peroxisome proliferation, an elevated level of H2O2in vivo, and total inhibition of the increased susceptibility to lipid peroxidation in vitro. No increase in lipid peroxidation in vivo was observed. Certain antioxidant enzymes (DT‐diaphorase, superoxide dismutase, glutathione transferase, glutathione peroxidase, and glutathione reductase) and components (ubiquinone and α‐tocopherol) were also measured. The results showed that there was some induction of these antioxidant enzymes and components by ASA or aminotriazole, except for glutathione peroxidase and superoxide dismutase, which were inhibited. The possible involvement of oxidative stress in the carcinogenicity of peroxisome proliferators

ISSN:0887-2082    

DOI:10.1002/jbt.2570100205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe Ah receptor (AhR) was visualized using monoclonal antibody Rpt 1 on protein blots of HeLa cell cytosol; two bands were detected at 104 and 106 kDa. The photoaffinity ligand, 2‐azido‐3‐[125I]iodo‐7,8‐dibromodibenzo‐p‐dioxin, was added to HeLa cells in culture, and after 1 hour the cells were UV irradiated. Cytosolic and high salt nuclear preparations were isolated and subjected to sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE), followed by transfer of the protein to membrane. The AhR was visualized on the membrane, revealing two bands. Alignment of an autoradiogram with the membrane revealed that only the 106 kDa (upper) band was photoaffinity labeled. The nuclear fraction contained only the photoaffinity‐labeled 106 kDa form of the AhR. The 104 kDa AhR does not appear to be a proteolytic product of the 106 kDa form. Cyanogen bromide fragmentation revealed that both forms contain the same sizeN‐terminal fragment. Sucrose density gradient analysis of HeLa cell cytosol indicated that both forms cosedimented at 9 S. Both the 106 and 104 kDa AhR bands were detected in four different human cell lines. Together, these results would indicate that the AhR in human cell lines exists

ISSN:0887-2082    

DOI:10.1002/jbt.2570100206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe arylhydrocarbon receptor (AhR) plays a central role in mediating 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) toxicity in animals. The investigations described here provide evidence that support a role for the AhR in TCDD‐mediated pyruvate carboxylase (PC) level/activity reductions in mice. Pyruvate carboxylase plays a pivotal role in gluconeogenesis and in supplying carbon units for the citric acid cycle. Delivered ip in a corn oil carrier, TCDD suppresses PC activity/amount at doses as low as 1 μg/kg in responsive C57BL/6J(Ahb/b) mice. Corn oil alone injected ip into mice at 4 mL/kg appears to be an inducer that increases the amount and activity of PC. However, TCDD suppresses this induction. In the Ahb/bmouse, PC levels and activity are reduced to 10% of control values at a dose of 75 μg/kg. A time‐course experiment shows that the PC reductions are apparent within 16 hours post‐TCDD exposure. Here we report investigations on the PC/TCDD response using a congenic C57BL/6J(Ahd/d) mouse strain having an AhR with a low affinity for TCDD. If the PC/TCDD response is AhR mediated, the congenic mouse strain (Ahd/d) would require much higher doses of TCDD to suppress PC. In the Ahd/dmice, we observe that an approximately 60‐fold increase in TCDD dose is necessary to produce a PC/TCDD effect. We also find that in Ahd/dmice, corn oil does not induce an increase in PC activity/amounts, as reporte

ISSN:0887-2082    

DOI:10.1002/jbt.2570100207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSoybean lipoxygenase‐mediated cooxidation of reduced glutathione (GSH) and concomitant superoxide generation was examined. The oxidation of GSH was dependent on the concentration of linoleic acid (LA), GSH, and the enzyme. The optimal conditions to observe maximal enzyme velocity included the presence of 0.42 mM LA, 2 mM GSH, and 50 pmole of enzyme/mL. The GSH oxidation was linear up to 10 minutes and exhibited a pH optimum of 9.0. The reaction displayed aKmof 1.49 mM for GSH andVmaxof 1.35 ± 0.02 μmoles/min/nmole of enzyme. Besides LA, arachidonic and γ‐linolenic acids also supported the lipoxygenase‐mediated GSH oxidation. Hydrogen peroxide and 13‐hydroperoxylinoleic acid supported GSH cooxidation, but to a very limited extent. Oxidized glutathione (GSSG) was identified as the major product of the reaction based on the depletion of nicotinamide‐adenine dinucleotide 3′‐phosphate (NADPH) in the presence of glutathione reductase. The GSH oxidation was accompanied by the reduction of ferricytochromec, which can be completely abolished by superoxide dismutase (SOD), suggesting the generation of superoxide anion radicals. Under optimal conditions, the rate of superoxide generation (measured as the SOD‐inhibitable reduction of ferricytochromec) was 10 ± 1.0 nmole/min/nmole of enzyme. These results clearly suggest that lipoxygenase is capable of oxidizing GSH to GSSG and simultaneously generating superoxide anion radicals, which may contribute to oxidative stress in cells under

ISSN:0887-2082    

DOI:10.1002/jbt.2570100208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570100209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570100201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY