Abstract:
:NADP(H)-dependent cytosolic aldo-keto reductases (AKR) are mostly monomeric enzymes which fold into a typical (α/β)(8)-barrel structure. Substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable loops (A, B, and C). Based on sequence identity, AKR have been grouped into families, namely AKR1-AKR15, containing multiple subfamilies. Two human enzymes from the AKR1B subfamily (AKR1B1 and AKR1B10) are of special interest. AKR1B1 (aldose reductase) is related to secondary diabetic complications, while AKR1B10 is induced in cancer cells and is highly active with all-trans-retinaldehyde. Residues interacting with all-trans-retinaldehyde and differing between AKR1B1 and AKR1B10 are Leu125Lys and Val131Ala (loop A), Leu301Val, Ser303Gln, and Cys304Ser (loop C). Recently, we demonstrated the importance of Lys125 as a determinant of AKR1B10 specificity for retinoids. Residues 301 and 304 are also involved in interactions with substrates or inhibitors, and thus we checked their contribution to retinoid specificity. We also extended our study with retinoids to rodent members of the AKR1B subfamily: AKR1B3 (aldose reductase), AKR1B7 (mouse vas deferens protein), AKR1B8 (fibroblast-growth factor 1-regulated protein), and AKR1B9 (Chinese hamster ovary reductase), which were tested against all-trans isomers of retinaldehyde and retinol. All enzymes were active with retinaldehyde, but with k(cat) values (0.02-0.52 min(-1)) much lower than that of AKR1B10 (27 min(-1)). None of the enzymes showed oxidizing activity with retinol. Since these enzymes (except AKR1B3) have Lys125, other residues should account for retinaldehyde specificity. Here, by using site-directed mutagenesis and molecular modeling, we further delineate the contribution of residues 301 and 304. We demonstrate that besides Lys125, Ser304 is a major structural determinant for all-trans-retinaldehyde specificity of AKR1B10.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Ruiz FX,Moro A,Gallego O,Ardèvol A,Rovira C,Petrash JM,Parés X,Farrés Jdoi
10.1016/j.cbi.2011.02.007subject
Has Abstractpub_date
2011-05-30 00:00:00pages
199-205issue
1-3eissn
0009-2797issn
1872-7786pii
S0009-2797(11)00065-2journal_volume
191pub_type
杂志文章abstract::Benzo[a]pyrene (BaP) undergoes metabolic transformation in mammals via oxidative, hydrolytic, and conjugative processes; however, little is known concerning BaP conjugation in freshwater algae. It has been shown in this laboratory that BaP is metabolized by Selenastrum capricornutum via a dioxygenase pathway. This stu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(90)90061-q
更新日期:1990-01-01 00:00:00
abstract::Levels of mixed-function oxidase (MFO) enzymes were measured in adriamycin(ADR)-sensitive murine leukemia P-388 and its ADR-resistant subline P-388/ADR. The subcellular fractions of the resistant cells showed decreased contents of MFO components, cytochrome P-450 and cytochrome b5, in comparison with the identically p...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(81)90067-3
更新日期:1981-04-01 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::Functional activity of neurotransmitter receptor and their sensitivity to regulation are altered in DM. We evaluated the neuroprotective effect of curcumin in glutamate mediated excitotoxicity in cerebral cortex of streptozotocin induced diabetic rats. Gene expression studies in diabetic rats showed a down regulation ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2012.11.024
更新日期:2013-01-25 00:00:00
abstract::Pyrazolone based metal complexes have strong bio-activity but the anti-cancer mechanism of these derivatives is not fully understood. In recent years, Cu(II) complexes have attracted the interest of researchers increasingly because of their high antitumor activities that are usually related to DNA binding. The reactio...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.08.022
更新日期:2015-10-05 00:00:00
abstract::Organophosphate (OP) based pesticides are highly toxic compounds that are still widely used in agriculture around the world. According to World Health Organization (WHO) data, it is estimated that between 250,000 and 370,000 deaths occur yearly around the globe as a result of acute intoxications by pesticides. Current...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.05.034
更新日期:2016-11-25 00:00:00
abstract::Aspirin is one of the oldest drugs and has been purported to have multiple beneficial effects, including prevention of cardiovascular disease and cancer, in addition to its original indication for treatment of inflammation, fever and pain. In cancer chemoprevention studies using animal models, two methods of aspirin a...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2008.10.008
更新日期:2009-05-15 00:00:00
abstract::Dioxinodehydroeckol (DHE) isolated from Ecklonia cava, has previously been investigated for its inhibition of the differentiation of 3T3-L1 preadipocytes into adipocytes. Levels of lipid accumulation were measured, along with changes in the expression of genes and proteins associated with adipogenesis and lipolysis. C...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.04.003
更新日期:2010-06-07 00:00:00
abstract::An assay of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GS) in crude extracts of cultured cells and tissues is described. It represents a novel combination of known methods, and is based on the formation of glutathione (GSH) from cysteine, glutamate and glycine in the presence of rat kidn...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(02)00017-0
更新日期:2002-04-20 00:00:00
abstract::S-(2,5-Dihydroxyphenyl)-cysteine and S-(2,5-dihydroxyphenyl)-N-acetyl-cysteine [the cysteine- and N-acetyl-cysteine adducts, respectively, of hydroquinone (HQ)] were identified and quantified in the urine of mice administered [ring-U-14C]acetaminophen [14C]APAP, 200 mg kg-1, i.p.). Urine was collected for 24 h and fra...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(88)90008-7
更新日期:1988-01-01 00:00:00
abstract::Catalytic scavengers of organophosphates (OPs) are considered very promising antidote candidates for preventing the adverse effects of OP intoxication as stand alone treatments. This study aimed at correlating the in-vivo catalytic efficiency ((kcat/KM)[Enzyme]pl), established prior to the OP challenge, with the sever...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.04.039
更新日期:2016-11-25 00:00:00
abstract::In isolated frog heart it was established that methylene-blue (MB, an oxidizing agent) decreased, while ascorbate (ASC, a reducing agent) increased the frequency of autorhythmic heart contractions. After MB treatment, in parallel with this phenomenon, the extracellular K+ concentration [K+]o showed a slow increase, bu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(87)90092-5
更新日期:1987-01-01 00:00:00
abstract::The peroxyl radicals CF3O2., CCl3O2. and CBr3O2. were produced by radiolysis of aerated aqueous-alcohol solutions of CF3Br, CF3Cl, CCl4 or CBr4. Kinetic spectrophotometric pulse radiolysis experiments were carried out in the presence of various substrates: urate, ascorbate, xanthine, hydroquinone, p-methoxyphenol, phe...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(87)90024-x
更新日期:1987-01-01 00:00:00
abstract::Resistance to chemotherapeutic agent is a major cause of treatment failure in patients with cancer. In many cases, the primaly mechanism leading to a multidrug-resistant phenotype is the plasma-membrane localized overexpression of drug efflux transporters, such as P-glycoprotein. However, acidic intracellular organell...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(01)00157-0
更新日期:2001-07-31 00:00:00
abstract::AKR1B10 is a human-type aldo-keto reductase. The up-regulation of AKR1B10 has been associated with various cancers including non-small cell lung carcinoma, viral and bacterial infections, and skin diseases. However, the mechanisms underlying AKR1B10 gene regulation are not fully understood. We previously indicated the...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2017.02.008
更新日期:2017-10-01 00:00:00
abstract::Malondialdehyde (MDA) in urine was measured as a 2,4-dinitrophenylhydrazine (DNPH) derivative using high-performance liquid chromatography (HPLC) for the analysis. MDA standard coeluted with a peak obtained from rat urine after i.p. administration of MDA standard. This peak was also the only peak containing 14C after ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(88)90070-1
更新日期:1988-01-01 00:00:00
abstract::Ethanol abuse is a serious public health problem that is associated with several stages of alcoholic liver disease (ALD) and a high incidence of morbidity and mortality. Alcoholic fatty liver disease (AFLD), the earliest stage of ALD, is a multifactorial injury that involves oxidative stress and disruptions of lipid m...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.10.003
更新日期:2016-12-25 00:00:00
abstract::The metabolism and genotoxicity of 1,2-dibromoethane (EDB) and its deuterium substituted analog ( d4EDB ) were studied in isolated rat hepatocytes. There was a marked isotope effect on the metabolism of EDB by hepatocytes. This was due to decreased microsomal oxidation of d4EDB . Cytosolic metabolism of EDB, as measur...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(84)90063-2
更新日期:1984-04-01 00:00:00
abstract::Epigallocatechin-3-gallate (EGCG), a tea polyphenol, inhibits the proliferation of many cancer cell lines; however, the antiproliferative mechanism(s) are not well-characterized. The objective of this study is to identify the cellular signaling mechanism(s) responsible for the antiproliferative effects of EGCG in the ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2007.09.001
更新日期:2008-01-10 00:00:00
abstract::Studies were undertaken to investigate the mechanism of bioactivation and covalent binding of TNT. Incubation of [14C]TNT with rat liver microsomes in the presence of an NADPH generating system resulted in metabolism and covalent binding to microsomal proteins. Time-dependence studies showed that TNT was rapidly reduc...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(94)03606-9
更新日期:1995-06-30 00:00:00
abstract::This study evaluates the possible protective effects of gallic acid (GaA) and ferulic acid (FeA) against an experimentally induced liver fibrosis by thioacetamide (TAA) in rats. Animals were divided into: Control group, GaA group (20 mg/kg/day, p.o), FeA (20 mg/kg/day, p.o), TAA group (receiving 250 mg/kg twice/week, ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2020.109098
更新日期:2020-06-01 00:00:00
abstract::The present study shows the existence of both Ca2+-dependent and EDTA-resistant hydrolysing activities against HDCP and paraoxon in the particulate and soluble fractions of hen, rat and rabbit liver. HDCP was more extensively hydrolysed than paraoxon in both subcellular fractions and each of three individuals of the t...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/s0009-2797(99)00035-6
更新日期:1999-05-14 00:00:00
abstract::Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity. Previous studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the mechanisms o...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2018.04.015
更新日期:2018-06-01 00:00:00
abstract::S1 nuclease hydrolysis and benzoylated naphthoylated DEAE cellulose (BND-cellulose) chromatography have been used to study the effect of riboflavin and visible light on DNA. Native calf thymus DNA was incubated with riboflavin in the presence of fluorescent light for various time periods and subjected to S1 nuclease h...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(84)90146-7
更新日期:1984-03-01 00:00:00
abstract::Interest in organoselenide chemistry and biochemistry has increased in the past three decades, mainly due to their chemical and biological activities. Here, we investigated the protective effect of the organic selenium compound diphenyl diselenide (PhSe)2 (5 μmol/kg), in a mouse model of methylmercury (MeHg)-induced b...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2013.08.002
更新日期:2013-10-25 00:00:00
abstract::The influence of systemic application of chemically unrelated drugs and xenobiotics (phenobarbital (PB), rifampicin (Rifa), pregnenolone-16 alpha-carbonitrile (PCN) and 3-methylcholanthrene (MC) on drug metabolizing enzymes was investigated in the skin of rats of both sexes. The results were compared with those obtain...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(80)90008-3
更新日期:1980-08-01 00:00:00
abstract::Due to its ability to inhibit the blood platelet PGHS-1, acetylsalicylic acid (ASA, Aspirin(®)) is widely used as a preventive agent in atherothrombotic diseases. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair effective ASA-mediated acetylation proce...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2016.04.021
更新日期:2016-06-25 00:00:00
abstract::Trypan blue at 50 microgram/ml stimulates the pinocytic uptake of 125I-labelled PVP, but not of colloidal 198Au or formaldehyde-denatured 125I-labelled bovine serum albumin, by the 17.5-day rat visceral yolk sac incubated in vitro. Neither Trypan blue nor a combination of the dye with 125I-labelled PVP stimulated the ...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(80)90097-6
更新日期:1980-11-01 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
doi:10.1016/0009-2797(90)90090-a
更新日期:1990-01-01 00:00:00
abstract::Human foreskin cell cultures in scheduled DNA synthesis (S phase) of the cell cycle were exposed to UV irradiation at a dose of 10 J . m-1 in the presence of insulin. These treated cell populations, when selectively passaged in a high amino acid supplemented complete growth medium (CM) after 20 Dulbecco's phosphate bu...
journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/0009-2797(81)90028-4
更新日期:1981-07-01 00:00:00