Abstract:
:Human serum paraoxonase/arylesterase (PON1, EC 3.1.8.1.) is a calcium-dependent enzyme which hydrolyzes a wide variety of organophosphates, including paraoxon, DFP, sarin and soman. Although the 3-D structure of PON has not yet been determined and its sequence shows no similarity with any other crystallized proteins, we undertook to identify some of its essential amino acid residues by two complementary approaches: group-specific labelling and site-directed mutagenesis. Group-specific labelling studies, performed on the purified native enzyme, indicated that one or more Trp, His and Asp/Glu are potentially important residues for PON activity. Based on these results, we identified some of these residues, conserved in the sequenced mammalian PON1, by site-directed mutagenesis. PON1 mutants were transiently expressed in 293T cells. The catalytic constants k(cat) and Km (relative to k(cat) and Km of the wild-type) determined with four different substrates (phenylacetate, paraoxon, diazoxon, chlorpyrifos oxon), were not significantly changed for the following mutants: W193A, W201A, W253A, H160N, H245N, H250N, H347N, E32A, E48A, D88A, D107A, D121A, D273A. By contrast, k(cat) was less than 1% for eight mutants: W280A, H114N, H133N, H154N, H242N, H284N, E52A and D53A. The essential amino acid residues identified in this work could be part of the PON1 active site, acting either as calcium ligands (E52 and D53?) or as substrate binding (W280?) or nucleophilic (His residues?) sites. However, we cannot rule out that the effects of mutations on catalytic properties resulted from a remote conformational change and/or misfolding of mutant proteins.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Josse D,Xie W,Masson P,Lockridge Odoi
10.1016/s0009-2797(99)00015-0subject
Has Abstractpub_date
1999-05-14 00:00:00pages
71-8eissn
0009-2797issn
1872-7786pii
S0009-2797(99)00015-0journal_volume
119-120pub_type
杂志文章abstract::Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments w...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2013.08.011
更新日期:2013-12-05 00:00:00
abstract::Incubation of Ca2(+)-loaded rat liver mitochondria with N-acetyl-p-benzoquinone imine (NAPQI) or its two dimethylated analogues resulted in a concentration dependent Ca2+ release, with the following order of potency: 2,6-(Me)2-NAPQI greater than NAPQI greater than 3,5-(Me)2-NAPQI. The quinone imine-induced Ca2+ releas...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
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abstract::Scoulerine, an isoquinoline alkaloid isolated from Corydalis plants, has been reported to possess potent anti-proliferative and pro-apoptotic function in cancer cells. However, the effects and underlying mechanisms of scoulerine on colorectal cancer (CRC) progression remain elusive. CCK-8 and LDH assays were used to e...
journal_title:Chemico-biological interactions
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doi:10.1016/j.cbi.2020.109184
更新日期:2020-08-25 00:00:00
abstract::Treatment of isolated mitochondria from rat hepatoma tumor cells (AS-30D) with the oxidant, t-butyl hydroperoxide (tBuOOH, 1 or 5 mumol/ml) resulted in the oxidation of glutathione (GSH to GSSG) and the formation of protein-glutathione mixed disulfides (ProSSG). The GSSG was retained inside of the hepatoma mitochondri...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(92)90073-t
更新日期:1992-09-28 00:00:00
abstract::The combined effects of ethanol and hypoxia on the conversion of xanthine dehydrogenase (D form) to xanthine oxidase (O form) and on the leakage of the enzyme from isolated rat hepatocytes was studied. Time-dependent death of cells occurred during incubation in hypoxic conditions. Ethanol (40 mM) had only a moderate e...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(92)90093-z
更新日期:1992-06-15 00:00:00
abstract::The effects of pH on access to the cytochrome P-450 active site, N-demethylation and formation of the cytochrome P-450 Fe(II)-RNO metabolite complex for a series of erythromycin derivatives were examined. Studies were performed with dexamethasone-treated rat liver microsomes containing large amounts of cytochrome P-45...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(92)90063-q
更新日期:1992-12-01 00:00:00
abstract::Changes in the rate of DNA synthesis in spermatogenic cells after treatment of segments of rat seminiferous tubule at defined stages of epithelial cycle with benzo[a]pyrene (BP) or 7,12-methylbenz[a]anthracene (DMBA) were studied. The incorporation of labeled thymidine into DNA was used as a measure of the rate of DNA...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
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更新日期:1989-01-01 00:00:00
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.09.009
更新日期:2018-12-25 00:00:00
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(97)00063-x
更新日期:1997-09-12 00:00:00
abstract::Glucosamine oligomers--monomer through tetramer--form complexes with Cu2+ that catalyse the hydrolysis of the 'nerve gas' 1,2,2-trimethylpropyl- methylphosphonofluroidate (soman) by cleaving the P-F bond. A 1/1 glucosamine/Cu2+ ratio whether as glucosamine or glucosamine units, gives the highest hydrolytic rate over t...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(93)90031-s
更新日期:1993-06-01 00:00:00
abstract::Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases, such as osteoporosis and rheumatic arthritis. Integrin αvβ3 abundantly expresses on osteoclast and plays a critical role in the formation and function of osteoclast, therefore, blockage of αvβ3 has become an attracti...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109179
更新日期:2020-08-25 00:00:00
abstract::The effect of repeated parenteral administration of cadmium (0.75, 1.5 and 3.0 mg/kg) on tissue disposition and urinary excretion of cadmium, zinc, copper and iron has been studied in the male rat. Cadmium, zinc and copper accumulated in liver and kidney, but the concentration of iron did not alter significantly. The ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90137-6
更新日期:1979-10-01 00:00:00
abstract::Experiments were conducted on the effects of various dose levels of benzo [a]pyrene (BP) on nuclear size in mouse interfollicular epidermis over a 3-day period. Topical application of BP was made with or without croton oil (CO) (0.1 or 0.5%) in the vehicles acetone, toluene and methyl ethyl ketone (MEK). Nuclear size ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90096-6
更新日期:1979-06-01 00:00:00
abstract::Normal reproductive development depends on the interplay of steroid hormones with their receptors at specific tissue sites. The concentrations of hormone ligands in the circulation and at target sites are maintained through coordinated regulation on steroid biosynthesis and degradation. Changed bioavailability of ster...
journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
doi:10.1016/j.cbi.2004.01.006
更新日期:2004-04-15 00:00:00
abstract::Oxidative stress is a major cause of drug induced hepatic diseases. The present study aims to investigate the antioxidative signaling mechanism of a protein isolated from the herb, Cajanus indicus against acetaminophen induced necrotic cell death. We found that incubation of hepatocytes with the protein prevented acet...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.09.006
更新日期:2009-01-27 00:00:00
abstract::The uptake and binding of ring-labelled [-14C]aflatoxin B1 (AFB1) by rat and hamster liver and kidney has been studied, the former species being extremely sensitive to the carcinogenic action of AFB, whereas the latter is resistant. In contrast to an earlier report (Lijinsky et al, Cancer Res., 30 (1970) 2280-2283, b...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(75)90019-8
更新日期:1975-08-01 00:00:00
abstract::Addition of the tumor promoter phorbol myristate acetate to polymorphonuclear leukocytes results in the oxidation of the arylamine carcinogens; [14C]benzidine, N-[14C]methylaminoazobenzene and [14C]aminofluorene to reactive intermediate(s) that bind irreversibly to the leukocyte DNA. The binding was dependent on oxyge...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(85)80081-8
更新日期:1985-02-01 00:00:00
abstract::American oysters (Crassostrea virginica) were exposed to 0.1 ppm cadmium for 0--15 days in a flowing seawater system and then placed into clean flowing seawater for 24 h prior to sacrifice. Whole oysters were homogenized and a cadmium-binding protein isolated and purified by a process of centrifugation, heat-treatment...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90041-3
更新日期:1979-05-01 00:00:00
abstract::Vitamin A-deficient male mice were treated for 10 days with 0.02% perfluorooctanoic acid (PFOA) in their diet. The effects of this highly potent peroxisome proliferator on peroxisomal palmitoyl-CoA oxidation and lauroyl-CoA oxidase activities were reduced by 3.1-7.5 times in comparison to the values obtained with mice...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(95)03630-5
更新日期:1995-10-20 00:00:00
abstract::To compare the effects of the food toxin 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and estradiol in hormone-responsive MCF-7 cells, the cells were exposed to different concentrations of either PhIP or estradiol. The effect of various culture conditions (e.g. phenol red, FBS, vehicle (DMSO/EtOH) and seedi...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.07.020
更新日期:2009-11-10 00:00:00
abstract::Benzene-induced hematopoietic toxicity is an aryl hydrocarbon receptor (AhR)-related adverse effect that is not exhibited in AhR-knockout (KO) mice. In the hematopoietic system, the steady-state expression of AhRs is limited in the hematopoietic progenitor cells; thus, a hierarchical hematopoietic impairment starts fr...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2009.12.022
更新日期:2010-03-19 00:00:00
abstract::The biotoxin okadaic acid (OA) is a lipophilic secondary metabolite of marine microalgae. Therefore, OA accumulates in the fatty tissue of various shellfish and may thus enter the food chain. The ingestion of OA via contaminated marine species can lead to the diarrhetic shellfish poisoning syndrome characterized by th...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.108937
更新日期:2020-02-01 00:00:00
abstract::The present study investigated the protective efficacy of dl-alpha-lipoic acid (LA) on adriamycin (ADR)-induced oxidative damage in rat testis. Adult male albino rats of Wistar strain were administered ADR (1 mg/kg body weight, i.v.), once a week for 10 weeks. ADR injected rats showed increased oxidative stress with a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2005.12.007
更新日期:2006-03-25 00:00:00
abstract::Environmental pollutant, Lead (Pb) is known to induce neurotoxicity in human. The central nervous system is the most vulnerable to the minute levels of Pb induced toxicity. Pb has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows epigenetic and developmental link associated with Alzheimer'...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2019.108927
更新日期:2020-01-25 00:00:00
abstract::DNA damage and DNA repair have been observed in cultured human skin fibroblasts exposed to potassium chromate but not to a chromic glycine complex. DNA repair synthesis (unscheduled incorporation of [3H]thymidine (TdR)) was measured in cells during or following exposure to chromate and was significant for chromate con...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90030-9
更新日期:1979-08-01 00:00:00
abstract::Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, which plays an important role on mediating myocardial injury. We tested the hypothesis that treatment with trimetazidine (TMZ) would improve Ca(2+)i handling in hypoxic myocardial injury. Cardiomyocytes isolated from neonat...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.04.022
更新日期:2015-07-05 00:00:00
abstract::The administration of cephaloridine to rats caused a decrease in the excretion of acid phosphatase into the urine. The antibiotic itself had no effect on urinary acid phosphatase and inhibitors or proteolytic enzymes were not present in the urine from treated rats. Cephaloridine may therefore be stabilizing the lysoso...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(79)90008-5
更新日期:1979-02-01 00:00:00
abstract::To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-b...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(88)90026-9
更新日期:1988-01-01 00:00:00
abstract::UDP-glucuronosyltransferases (UGTs) are a family of phase II drug metabolizing enzymes that catalyze glucuronidation of numerous endogenous and exogenous substrates. Carbon tetrachloride (CCl4) is widely used to develop liver injuries mimicking human liver diseases. However, effects of CCl4 on the expression and activ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109115
更新日期:2020-07-01 00:00:00
abstract::Vitamin A (retinoids) has an essential role in development and throughout life of humans and animals. Consequently, effects of the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid metabolism may be contributory to its toxicity. This study was performed to clarify the mechanism behind diox...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(02)00157-6
更新日期:2003-03-06 00:00:00