摘要:

AbstractStudies were carried out to evaluate the effects of cadmium in vitro on microsomal steroid metabolism in the inner (zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex. Microsomes from the inner zone have greater 21‐hydroxylase than 17α‐hydroxylase activity, resulting in the conversion of progesterone primarily to 11‐deoxycorticosterone and of 17α‐hydroxy progesterone principally to its 21‐hydroxylated metabolite, 11‐deoxycortisol. Microsomes from the outer zones, by contrast, have far greater 17α‐hydroxylase and C17,20‐lyase activities than 21‐hydroxylase activity. As a result, progesterone is converted primarily to its 17‐hydroxylated metabolite, 17α‐hydroxyprogesterone; and 17α‐hydroxyprogesterone is converted principally to δ4‐androstenedione, with only small amounts of 21‐hydroxylated metabolites being produced. Addition of cadmium to incubations with inner zone microsomes causes concentration‐dependent decreases in 21‐hydroxylation and increases in 17α‐hydroxylase and C17,20‐lyase activities, resulting in a pattern of steroid metabolism similar to that in normal outer zone microsomes. Cadmium similarly decreases 21‐hydroxylation by outer zone microsomes but has no effect on the formation of 17‐hydroxylated metabolites or on androgen (Δ4‐androstenedione) production. In neither inner nor outer zone microsomes did cadmium affect cytochrome P‐450 concentrations, steroid interactions with cytochrome(s) P‐450, or NADPH–cytochrome P‐450 reductase activities. The results indicate that cadmium produces both quantitative and qualitative changes in adrenal microsomal steroid metabolism and that the nature of the changes differs in the inner and outer adrenocortical zones. In inner zone microsomes, there appears to be a reciprocal relationship between 21‐hydroxylase and 17α‐hydroxylase/C17,20‐lyase activitie

ISSN:0887-2082    

DOI:10.1002/jbt.2570020102

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

年代:1987

数据来源: WILEY

摘要:

AbstractNuclear uptake and chromatin binding of nickel(II) was investigated in Chinese hamster ovary (CHO) cells. The cytoplasmic:nuclear ratio of nickel immediately following treatment was 5:1, but by 24 and 48 hours this ratio decreased to 4:l and 2:1, respectively, indicating that nickel is retained longer in the nucleus than cytoplasmic nickel. Chromatin was fractionated by sonication and centrifugation into fast‐sedimenting, magnesium‐insoluble, or magnesiumsoluble components. The magnesium‐insoluble portion bound more nickel ions and retained the metal longer than either the magnesium‐soluble or the fastsedimenting fractions. Treatment of cells with nickel chloride (NiCl2) decreased the amount of DNA in the magnesium‐insoluble fraction but increased the amount of DNA in the fast‐ sedimenting chromatin fraction. The magnesium‐insoluble fraction isolated from nickel‐treated cells contained approximately ten times more [35‐S]‐methionine–labeled protein per milligram DNA compared with untreated cells. The magnesium‐soluble and the fast‐sedimenting fractions isolated from the nickel‐treated cells did not exhibit a similar increase in [35‐S]‐methionine–labeled protein per milligram of DNA. Nickel treatment suppressed [14‐C]‐thymidine incorporation into total DNA by 30% compared with untreated cells. However, the magnesium‐insoluble chromatin fraction from nickel‐treated cells had a tenfold to 20‐fold increase in thymidine incorporation, while the other chromatin fractions did not exhibit an increase in thymidine incorporation. These findings indicate that nickel induced widespread alterations in chromatin conformation and preferentially interacted

ISSN:0887-2082    

DOI:10.1002/jbt.2570020103

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

年代:1987

数据来源: WILEY

摘要:

AbstractPurifiedTorpedo nobilianaelectric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)‐stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3‐H]‐phencyclidine ([3‐H]‐PCP) binding to the channel sites, acting as a weak agonist. The activation of [3‐H]‐PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb‐activated [3‐H]‐PCP binding with Kivalues of 10, 20, and 1,600 μM, respectively. The inhibition was mixed competitivenoncompetitive in nature. The characteristic response of CRPVF to carb‐stimulated [22‐Na] influx was inhibited by the three carbamates, with IC‐50 values of 6,50, and 1,000 μM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb‐stimulated [22‐Na]influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125‐I]‐α‐ bungarotoxin ([125‐I]‐α‐BGT) with the following decreasing order of potency: Neo

ISSN:0887-2082    

DOI:10.1002/jbt.2570020104

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

年代:1987

数据来源: WILEY

摘要:

AbstractChlordecone greatly potentiates carbon tetrachloride (CC14) hepatotoxicity. In order to quantitate the degree of this potentiation, the effects of a range of doses of CC14on two microsomal enzymatic functions and liver enzyme release were examined in chlordecone‐treated and control rats. Male Sprague‐Dawley rats were pretreated with 15 mg chlordecone per kilogram body weight (BW) intragastrically or with vehicle. After 48 hours, 0 to 250 μ1 CC14per 100 g body weight were given intraperitoneally (IP), and the rats were killed 24 hours later. Chlordecone treatment produced approximately a 17‐fold potentiation of the CC14dependent loss of cytochrome P‐450 and glucose‐6‐phosphatase activity, so that a dose of 6 μ1 CC14per 100 g body weight in the chlordecone‐treated animals resulted in a similar amount of damage as observed with 100 μ1 CC14per 100 g body weight in controls. A similar potentiation by chlordecone was seen with CC14‐ induced increases in serum glutamic‐oxaloacetic transaminase (SGOT) levels. Chlordecone treatment also increased hepatic cytochrome P‐450 levels by 67% and resulted in an increase in the covalent binding of [14‐C]‐CC14‐derived metabolites to microsom

ISSN:0887-2082    

DOI:10.1002/jbt.2570020105

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

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of chlordecone (CD) on hepatic repair, measured either as recovery of microsomal enzymatic functions or as the induction of cytosolic thymidine kinase (TK) activity, was evaluated in rats given carbon tetrachloride (CC14). Carbon tetrachloride was administered to CD‐potentiated and control animals using doses of this hepatotoxin which produce similar degrees of damage at 24 hours in both groups of animals (6 and 100 μ1 CC14per 100 g body weight, respectively). Chlordecone had no significant effect on the time course of recovery of microsomal cytochrome P‐450 content or glucose‐6‐phosphatase activity following CC14administration. Hepatic TK activity was measured 48 hours after CC14administration as a biochemical index of the hepatic regenerative response. Thymidine kinase activity was increased eightfold in CD‐treated rats receiving 6 μ1 CC14per 100 g body weight, whereas in controls a similar induction of TK activity was produced by 100 μ1 CC14per 100 g body weight. Therefore, the TK response in CD‐treated rats receiving CC14is appropriate for the amount of damage produced, suggesting that CD does not inhibit the hepatic regenerative response to CC14‐induced injury. The effect of CD on hepatic repair was also examined in rats receiving a two‐thirds partial hepatectomy. Pretreatment of animals with CD had no significant effect on the increase in TK activity produced 24 hours after partial hepatectomy. These results offer no support for the idea that CD impairs hepatic repair after either partial hepatectomy or

ISSN:0887-2082    

DOI:10.1002/jbt.2570020106

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

年代:1987

数据来源: WILEY

摘要:

AbstractOut of the three cadmium‐binding proteins (CD‐BPs) in rat liver parenchyma (40K, 29K, and 24K CdBPs), the 40K Cd‐BP showed the highest affinity for cadmium (Cd), with a dissociation constant (KD) of 1.2 × 10−8M. This is in between the affinity of human serum albumin KD= 3.8 × 10−5M) and metallothionein (KD =<10−11). These Cd‐BPs may be responsible for hepatic sequestra

ISSN:0887-2082    

DOI:10.1002/jbt.2570020107

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

年代:1987

数据来源: WILEY

ISSN:0887-2082    

DOI:10.1002/jbt.2570020101

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

年代:1987

数据来源: WILEY