摘要:

AbstractExpression of house fly cytochrome P‐450lprwas examined using immunoblotting in male and female adult LPR house flies, mixed sex adult house flies at 12 different ages, larvae, and pupae. P‐450lprwas expressed in both male and female adult house flies. P‐450lprwas clearly present in all adult stages examined, was barely detectable in pupae, and could not be detected in larvae. Thus, cytochrome P‐450lpris developmentally regulated and present in both sexes of house fly.Expression of cytochrome P‐450, immunologically homologous to house fly cytochrome P‐450lprwas examined in other species using immunoblot analysis. Eleven animal species were tested in the orders Diptera, Hymenoptera, Lepidoptera, Orthoptera, Acari, and Rodentia, using microsomes in some species from both induced and noninduced animals or insecticide‐resistant and susceptible strains. P‐450lprappears to be restricted to house flies, as none of these species contained cytochrome P‐450 that reacted with antiserum to cy

ISSN:0887-2082    

DOI:10.1002/jbt.2570060402

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

年代:1991

数据来源: WILEY

摘要:

AbstractHuman erythrocytes exposed to 0.1 mM tellurite (K2TeO3) in an isotonic buffered choline chloride medium for 15 min at 37°C, washed, and incubated further in the absence of the chemical in the buffer, exhibited selective leakiness for potassium within minutes. The potassium efflux curve was sigmoidal, with an initially slow leakage followed by a sharp rise (first‐order kinetics) and a plateau by 60 min. After 15 min, 30–50% of the total potassium concentration had leaked from the cells, although less than 1% lysis had occurred. The control cells incubated in buffer with no K2TeO3exhibited no potassium leakage. The mean volume of the K2TeO3‐treated erythrocytes increased and their median density decreased, indicating changes in the colloid osmotic state and physical characteristics of the cells. However, cells pretreated with K2TeO3exhibited no significant change in glutathione (GSH) concentration and no membrane lipid peroxidation, unlike cells pretreated witht‐butylhydroperoxide (Deutickeet al., Biochim. Bio phys. Acta, 899, 125–128, 1987). The enhanced potassium permeability of the K2TeO3‐treated erythrocytes preceded the increase in cell volume, intracellular hydration, and a decrease in median density. We suggest that perturbation of the lipid‐protein interaction in the membrane by the oxidant alters the potassium permeability and results in the selective leakage with even

ISSN:0887-2082    

DOI:10.1002/jbt.2570060403

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe relationship between the covalent binding, uptake, and toxicity produced by pentachlorobutadienyl‐L‐cysteine (PCBC) was examined in rabbit renal proximal tubules (RPT), renal basolateral membrane vesicles, and isolated renal cortical mitochondria. Renal proximal tubules rapidly metabolized PCBC to a reactive intermediate that bound to tubular protein. Approximately 70–90% of PCBC found in the cell at any given time was bound to protein. PCBC initially uncoupled oxidative phosphorylation, followed by a 45% reduction of state 3 respiration and a 90% decrease in cellular adenosine triphosphate (ATP) levels. These events preceded cell death. Isolated mitochondria also metabolized PCBC to a reactive intermediate that bound to mitochondrial protein and initiated mitochondrial toxicity. These results show that. PCBC‐induced mitochondrial dysfunction occurred as a result of mitochondrial bioactivation and that the mitochondrion is the critical subcellular target in PCBC toxicity. Aminooxyacetic acid (AOAA), an inhibitor of cysteine conjugate β‐lyase, reduced the covalent binding of PCBC‐equivalents to tubular protein by approximately 90% and decreased but did not prevent the toxic effects produced by PCBC on RPT respiration and cellular ATP levels. AOAA delayed but had no effect on the overall extent of cell death produced by PCBC. The protective effect of AOAA was independent of any effects on PCBC uptake. These results show that AOAA decreased but did not prevent the metabolism of PCBC by cysteine conjugate β‐lyase. The partial inhibition of PCBC metabolism, and hence, PCBC‐induced cell death by AOAA, may be related to limited concentrations of AOAA within the tubule cel

ISSN:0887-2082    

DOI:10.1002/jbt.2570060404

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

年代:1991

数据来源: WILEY

摘要:

AbstractWe studied the effects of acute and chronic in vivo inhibition of acetylcholinesterase on both the density and function of brain muscarinic cholinergic receptors. Adult male rats were treated either once or multiple times over a period of 10 days with the irreversible acetylcholinesterase inhibitor diisopropylfluorophosphate (DFP). The concentration and affinity of muscarinic receptors in various brain regions were determined using radioligand binding techniques. Acute DFP treatment resulted in a significant reduction in receptor number only in the brain stem, while chronic treatment caused receptor downregulation in the brain stem, cerebral cortex, and striatum. There was no change in ligand affinity in any of the brain regions. In sharp contrast, muscarinic receptor function was fully preserved, in terms of coupling of the receptors to increased phosphoinositide hydrolysis in the cerebral cortex, hippocampus, and striatum, or inhibition of cyclic AMP formation in the cerebral cortex or striatum. Therefore, there is a marked lack or correlation between DFP‐induced muscarinic receptor down‐regulation and receptor desensitizat

ISSN:0887-2082    

DOI:10.1002/jbt.2570060405

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe molecular mechanisms governing the increased cell surface expression of major histocompatibility complex (MHC) class II molecules (Ia) on lead‐treated mouse B cells was investigated. Lead has been shown to directly cause a selective, two‐fold increase in the B cell's surface density of both products of the I region of the mouse MHC, I‐A and I‐E. In the present study, Western blot analysis showed that Pb increases the total cellular pool of I‐A β‐chain by twofold. The increase in cellular I‐A was not found to be due to increased messenger RNA (mRNA) for either the α‐ or the β‐chain of I‐A. Biosynthetic labeling studies showed that Pb increases the translation or the stability of the Ia‐associated invariant chain (Ii or γ) and possibly the β‐chain of Ia. Collectively these results suggest that Pb increases the B cell's surface Ia by influencing translational or posttranslational regulation of Ia

ISSN:0887-2082    

DOI:10.1002/jbt.2570060406

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe effect of highly purified rat liver cytosolic NAD(P)H‐quinone oxidoreductase [EC 1.6.99.2] on the mutagenicity of 1,3‐ 1,6‐ and 1,8‐dinitropyrene (DNP) was studied in the AmesSalmonella typhimuriummutagenicity assay. NAD(P)H‐quinone oxidoreductase over the range of 0.02–0.8 μ g/plate (38–1500) units increased up to threefold the mutagenicity of all three DNPs inS. typhimuriumTA 98. In TA98NR, a strain deficient in “classical” nitroreductase, the mutagenicity of 1,6‐ and 1,8‐DNP was essentially unchanged, whereas that of 1,3‐DNP was markedly reduced. NAD(P)H‐quinone oxidoreductase enhanced the mutagenicity of 1,6‐ and 1,8‐DNP to approximately equivalent extents in TA98NR and TA98. The mutagenicity of 1,3‐DNP in TA98NR was potently enhanced by the addition of NAD(P)H‐quinone oxidoreductase in a dose‐responsive manner. In the presence of 0.8 μg NAD(P)H‐quinone oxidoreductase, 1,3‐DNP displayed a mutagenic response in TA98NR that was comparable to that obtained in TA98. NAD(P)H‐quinone oxidoreductase was found to increase the mutagenicity of 1,6‐ but not 1,3‐ or 1,8‐DNP to mutagenic intermediates in TA98/1,8‐DNP6, a strain deficient inO‐acetyltransferase activity. The results suggest that NAD(P)H‐quinone oxidoreductase not only catalyzes reduction of the parent DNP but also that of partially reduced metabolites generated from that DNP. Such reductive metabolism may lead to i

ISSN:0887-2082    

DOI:10.1002/jbt.2570060407

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe interaction of avermectin B1a(AVMB1a) with mouse brain chloride channels was characterized using a radiochloride efflux assay. The loss of intravesicular chloride from synaptoneurosomes preloaded with36Cl involved an initial rapid phase followed by a slower phase that approached equilibrium within 10 min. AVMB1astimulated a 30% loss of intravesicular chloride within the first 2 s of exposure; however, AVMB1ahad no effect on the rate of the slower phase of chloride loss. Experiments with lysed synaptoneurosomes showed that both chloride loading and basal and AVMB1a‐stimulated chloride release required the presence of intact vesicles. The efflux of36Cl from mouse brain synaptosomes and the stimulation of efflux by AVMB1awere qualitatively similar to the results obtained with synaptoneurosomes but involved much lower overall levels of chloride loading and release. AVMB1aproduced halfmaximal stimulation of chloride efflux from synaptoneurosomes at a concentration of 2.1 ± 0.3 μM and a 35.4 ± 1.4% maximal loss of intravesicular chloride at saturating concentrations. γ‐Aminobutyric acid (GABA), bicuculline, or the chloride channel blockers picrotoxinin,t‐butylbicyclophosphorothionate (TBPS) 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS), and anthracene 9‐carboxylic acid (9‐CA) had little or no effect on the loss of chloride from synaptoneurosomes either in the presence or the absence of AVMB1a. However, the chlorinated cycloalkane insecticides dieldrin and lindane were equally effective as inhibitors of GABA‐dependent chloride uptake and AVMB1a‐stimulated chloride efflux. These data demonstrate that AVMB1a‐stimulated chloride efflux from mouse brain synaptic vesicles results from the activation of GABA‐insensitive chloride channels and that this action is distinct from their previously documented effects on GABA‐gated chloride channels in mouse brain preparations. Our findings imply that both GABA‐gated and GABA‐insensitive chloride channels may be toxicologically significant

ISSN:0887-2082    

DOI:10.1002/jbt.2570060408

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

年代:1991

数据来源: WILEY

摘要:

AbstractMercuric ion, a well‐known nephrotoxin, promotes oxidative tissue damage to kidney cells. One principal toxic action of Hg(II) is the disruption of mitochondrial functions, although the exact significance of this effect with regard to Hg(II) toxicity is poorly understood. In studies of the effects of Hg(II) on superoxide (O 2−) and hydrogen peroxide (H2O2) production by rat kidney mitochondria, Hg(II) (1–6 μM), in the presence of antimycin A, caused a concentration‐dependent increase (up to fivefold) in mitochondrial H2O2production but an apparent decrease in mitochondrial O 2−production. Hg(II) also inhibited O 2−‐dependent cytochrome c reduction (IC50≈︁2–3 μM) when O 2−was produced from xanthine oxidase. In contrast, Hg(I) did not react with O 2−in either system, suggesting little involvement of Hg(I) in the apparent dismutation of O 2−by Hg(II). Hg(II) also inhibited the reactions of KO2(i.e., O 2−) with hemin or horseradish peroxidase dissolved in dimethyl sulfoxide (DMSO). Finally, a combination of Hg(II) and KO2in DMSO resulted in a stable UV absorbance spectrum [currently assigned Hg(II)‐peroxide] distinct from either Hg(II) or KO2. These results suggest that Hg(II), despite possessing little redox activity, enhances the rate of O 2−dismutation, leading to increased production of H2O2by renal mitochondria. This property of Hg(II) may contribute to the oxidativ

ISSN:0887-2082    

DOI:10.1002/jbt.2570060409

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe effect of intracellular calcium chelators on rabbit renal proximal tubule (RPT) cell death induced byt‐butyl hydroperoxide (TBHP) and H2O2was examined. Preincubation of RPT suspensions with 50 μM QUIN 2/AM completely prevented TBHP (0.5 mM) and H2O2(2 mM) induced cell death [i.e., release of lactate dehydrogenase (LDH)]. QUIN 2/AM, BAPTA/AM, EGTA/AM, and FURA 2/AM, at 5 μM, decreased LDH release (at 6 hr) from 41% to 4%, 21%, 26%, and 33%, and decreased lipid peroxidation (at 1 hr) from 1.0 to 0.1, 0.4, 0.6, and 0.8 nmol MDA/mg protein, respectively, after TBHP exposure. Since oxidant‐induced lipid peroxidation and cell death are iron‐dependent in this model, these results suggest that the intracellular calcium chelators inhibit cell death by chelati

ISSN:0887-2082    

DOI:10.1002/jbt.2570060410

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

年代:1991

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570060411

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

年代:1991

数据来源: WILEY