Disease relevance of CES1

• Expression of human TGH in Escherichia coli yields a protein without enzymatic activity, which suggests that posttranslational processing is necessary for the catalytic activity [1].
• Expression of hTGH with its native signal sequence and a C-terminal 6xHis-tag in Sf9 cells using the baculovirus expression system yielded active enzyme [2].
• The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study [3].
• In contrast, Phe-OMe toxicity for myeloid cells was found to correlate with serine esterase-mediated intracellular trapping of high concentrations of the free amino acid Phe [4].
• A novel membrane-bound serine esterase in human T4+ lymphocytes immunologically reactive with antibody inhibiting syncytia induced by HIV-1. Purification and characterization [5].

High impact information on CES1

• On the basis of these observations, we suggest that some CES-2/PAR family transcription factors are evolutionary conserved regulators of programmed cell death [6].
• The CES-2 protein is most similar to members of the PAR (proline- and acid-rich) subfamily of bZIP proteins and has DNA-binding specificity like that of PAR-family proteins [6].
• Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway [7].
• Northern blots show that gamma/delta T cells express perforin, serine esterase 1 (SE 1), and SE 2 [8].
• Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced [9].

Chemical compound and disease context of CES1

• A novel membrane-bound serine esterase, named tryptase TL2, which is immunologically reactive with the antibody inhibiting induction of syncytia by human immunodeficiency virus-1 (HIV-1) (Hattori, T., Koito, A., Takatsuki, K., Kido, H., and Kutunuma, N. (1989) FEBS Lett., 248, 48-52), has been purified from a human T4+ lymphocyte clone [5].
• Acyl CoA: cholesterol acyltransferase (ACAT) inhibitors are known to inhibit cholesterol absorption and are under investigation to reduce hypercholesterolemia [10].
• We demonstrate that a serine esterase inhibitor provides some protection from the toxicity of epoxy fatty esters to sEH expressing cells as do intercellular free sulfhydryls, but that this protection is not due to glutathione conjugation [11].
• The present results indicate that the magnitude of anaphylactic histamine release from human skin does not match that of the activation of serine esterase in the reaction, suggesting the possibility that there may be some factor modulating the activation of serine esterase in the anaphylactic reaction in human skin [12].
• The serine esterase TL2 from human T4+ lymphocytes is a binding component to HIV-1 glycoprotein gp120 and seems to play a role in the HIV-1 infection mechanism [13].

Biological context of CES1

• Relative CES1 and CES2 expression levels were determined by reverse transcription of the respective mRNAs, followed by polymerase chain reaction amplification [14].
• Human carboxylesterases 1 and 2 (CES1 and CES2) catalyze the hydrolysis of many exogenous compounds [15].
• We resequenced CES1 and CES2 in multiple populations (n = 120) to identify single-nucleotide polymorphisms and confirmed the novel SNPs in healthy European and African individuals (n = 190) [15].
• Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction [16].
• Their coding sequences showed high homology, with only four amino acid differences in the N-terminal region, but our sequencing study of the 5' regions revealed that CES1A1 and CES1A2 had distinctive consensus sequences for transcription factors in the regions, implying differences in transcriptional regulation of the genes [17].

Anatomical context of CES1

• Co-expression of CES1 and BSEP partly protected oocytes from this toxic effect [18].
• cDNA cloning and characterization of human monocyte/macrophage serine esterase-1 [19].
• Human monocyte/macrophage serine esterase (HMSE), commonly known as acid esterase or alpha-naphthylacetate esterase, comprises a group of five enzyme variants that can be distinguished by their isoelectric points from esterase variants of the other normal human blood cell populations [19].
• A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases [20].
• Cholesteryl ester hydrolase (CEH) is responsible for hydrolysis of stored cholesterol esters in macrophage foam cells and release of free cholesterol for high-density lipoprotein-mediated efflux [21].

Associations of CES1 with chemical compounds

• Simple butyl and pentyl, but not ethyl, carbamate prodrugs inhibited the growth of cancer cells that overexpress carboxylesterase CES1 (hCE1) and CES2 (hiCE) [14].
• CES1 catalytic efficiency was 2-fold higher with 5' phenylalanyl monoesters than the corresponding 3' esters of floxuridine [22].
• We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication [23].
• After methylselenocysteine treatment, the intratumor area under the concentration-time curve of SN-38 increased to a significantly higher level in A253 than in FaDu and was associated with increased expression of CES1 in both tumors [24].
• The amino acid composition of the putative active site of HMSE1 as deduced from the nucleotide sequence corresponds with the active sites of other serine esterases but not with the active sites of serine proteases [19].

Physical interactions of CES1

• Pretreatment of neutrophils with serine esterase inhibitors did not abrogate binding capacity of the cells for C1-INH, whereas the binding affinity for C1-INH was lost when the cells were pretreated with trypsin [25].

Regulatory relationships of CES1

• A serine esterase inhibitor blocked this activity and a recombinant PON1 was devoid of it, raising the possibility that the activity represents platelet-activating factor acetylhydrolase (PAF-AH), an esterase that co-purifies with PON1 from HDL [26].
• We show evidence that both PAF acetylhydrolase (PAF-AH) and transacetylase activities are inhibited to the same extent by serine esterase inhibitors, are resistant to heat treatment, and exhibit identical distributions in lipoprotein classes and in LDL subfractions [27].
• The activity of leukocyte migration inhibitory factor (LIF) obtained from Sephadex-G-100-chromatographed supernatants of concanavalin-A-stimulated human lymphocytes was suppressed by two synthetic serine esterase and serine protease inhibitors (di-isopropylfluorophosphate (DFP) and phenylmethylfulfonyl fluoride (PMSF)) [28].

Other interactions of CES1

• Accordingly, the kinetics of hydrolysis of individual enantiomers by purified native and recombinant human liver carboxylesterases CES1A1 and CES2 and a colon isoenzyme CES3 were examined with a liquid chromatography/mass spectrometry assay [29].
• Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site [1].
• METHODS: We evaluated monocytic differentiation markers (CD11b, CD14, and monocytic serine esterase), cell cycle parameters, and cell proliferation rates after treatment of cells with different agents with or without carnosic acid [30].
• IL-2 restored the lytic potential and serine esterase activity to normal values within 72 h [31].
• In contrast, a serine esterase inhibitor abolished phospholipase activity even though PON1 has no active-site serine residues [32].

Analytical, diagnostic and therapeutic context of CES1

• The 1941-bp cDNA differs by only a few bases from two previously reported cDNAs for human liver carboxylesterase, allowing the anti-human carboxylesterase antiserum to be used for immunoprecipitation of human egasyn [16].
• When these cells were incubated in lipoprotein-deficient serum for 18 hours, the mRNA for ACAT/carboxylesterase was almost not detectable on Northern blots, whereas after incubation with acetylated low-density lipoproteins, a strong hybridization signal was obtained [33].
• The sensitive technique of RT-PCR was used to identify cholesteryl ester hydrolase (CEH) expressed in human macrophages [34].
• In the present study, to investigate the transcriptional regulation of the promoter region of the CES1 and CES2 genes were isolated from mouse, rat and human genomic DNA by PCR amplification [35].
• We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy [3].

References