Carboxylesterase 1 (Ces1): from monocyte marker to major player

Markey, G. M.

doi:10.1136/jcp.2010.084657

Cited by 21 publications

(15 citation statements)

References 37 publications

(28 reference statements)

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“…The role of the CES1 gene in SS pathogenesis warrants further investigation. CES1 has been linked to the pathogenesis of non-Hodgkin’s lymphoma, possibly involving a mechanism by which the downregulation or deficiency in CES1 reduces the ability of macrophages to kill cancer cells [ 51 ]. In addition, patients with SS are 44 times more susceptible to developing non-Hodgkin’s lymphoma compared to the normal population [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Biosemantics guided gene expression profiling of Sjögren’s syndrome: a comparative analysis with systemic lupus erythematosus and rheumatoid arthritis

et al. 2017

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BackgroundSjögren's syndrome (SS) shares many clinical and pathological similarities with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These autoimmune diseases mostly affect women. In this study, concept profile analysis (CPA) and gene expression meta-analysis were used to identify genes potentially involved in SS pathogenesis.MethodsHuman genes associated with SS, SLE, and RA were identified using the CPA tool, Anni 2.1. The differential mRNA expression of genes common to SS and SLE (SS-SLE) was determined in female peripheral blood mononuclear cells (PBMCs) using NCBI-GEO2R. Differentially expressed (DE) SS-SLE PBMC genes in common with the SS-SLE CPA-identified genes were analyzed for differential expression in salivary glands or synovial biopsies, and for genes common to SS and RA and SLE and RA, analyzing differential expression in salivary glands in SS, synovial fibroblasts in RA, and synovial fluid in SLE. Among common genes, DE genes found in salivary gland mRNA expression in patients with SS were used for gene enrichment and SS molecular network construction. Secondary analysis was performed to identify DE genes unique to the disease site tissues, by excluding PBMC and CPA common DE genes to complement the SS network.ResultsWe identified 22 DE genes in salivary gland datasets in SS that have not previously been clearly associated with SS pathogenesis. Among these, higher levels of checkpoint kinase 1 (CHEK1), V-Ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1), and lymphoid enhancer binding factor 1 (LEF1) were significantly correlated with higher matrix metalloproteinase 9 (MMP9) levels. Higher MMP9 levels have been implicated in degradation of salivary gland structural integrity, leading to hypo-salivation in patients with SS. Salivary gland mRNA expression of MMP9 and the expression of cytokine CXCL10 were higher in patients with SS. CXCL10 has been shown to increase MMP9 expression and therefore may also play an important role in SS pathogenesis.ConclusionUsing CPA and gene expression analysis, we identified factors targeting MMP9 expression and/or function, namely CHEK1, CXCL10, ETS1, LEF1, and tissue inhibitor of metalloproteinase 1; altered mRNA expression of these could increase expression/activity of MMP9 in a concerted manner, thereby potentially impacting SS pathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1400-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Biosemantics guided gene expression profiling of Sjögren’s syndrome: a comparative analysis with systemic lupus erythematosus and rheumatoid arthritis

et al. 2017

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“…Following oral administration, quinapril and enalapril are hydrolysed to the active diacid metabolites quinaprilat (about 40% of an oral dose) and enalaprilat (about 60% of an oral dose) [2,[4][5][6][7][8]. This bioactivation is catalysed mainly by carboxylesterase 1 (CES1) [9,10], an αβ-hydrolase fold enzyme expressed in various tissues, such as the liver, lungs and adipose tissue, but not in plasma [11][12][13][14]. A single nucleotide variation (SNV) in the CES1 gene (NM_001025194.1:c.428G > A, p.G143E, rs71647871) has been associated with reduced activity of CES1 in vitro and reduced biotransformation of CES1 substrate drugs, such as methylphenidate, oseltamivir and clopidogrel, in vivo in humans [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Tarkiainen

Tornio

Holmberg

et al. 2015

Brit J Clinical Pharma

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AIMThe aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers. METHODSIn a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h. RESULTSThe area under the plasma concentration-time curve from 0 h to infinity (AUC 0-∞ ) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC 0-∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril. CONCLUSIONSThe CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Quinapril and enalapril are prodrugs that are hydrolysed in the liver to active metabolites by carboxylesterase 1 (CES1).• The CES1 c.428G > A SNV markedly decreases CES1 activity.• There appear to be no previous studies of the effect of CES1 c.428G > A SNV on the pharmacokinetics of ACE inhibitors in humans. WHAT THIS STUDY ADDS• The CES1 c.428G > A SNV significantly reduced the hydrolytic activation of enalapril, but had no observable effect on quinapril.• These data suggest that CES1 genetic variants can affect the pharmacokinetics of angiotensin-converting enzyme (ACE) inhibitors in humans, and that ACE inhibitors differ in their susceptibility to the effects of CES1 genetic variants.

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“…This study indicated that the immune-related genes included chemokine-related genes (CXCL9, CX3CR1, and CCL5), B-cell antigen-binding-related genes (IGHD, IGHM, IGKC, LOC652493, IGK@, and GPR183), detoxification by carboxylesterase 1 in the liver and monocytes (41), granzyme family for proapoptic protease (42), initiator of allergic reaction (FCER1A) (43), and C3 (complement for danger signal) (44). Recent studies have shown that CX3CR1 is related to the development of periapical lesions.…”

Section: Discussionmentioning

confidence: 97%

Comparative Gene Expression Analysis of the Coronal Pulp and Apical Pulp Complex in Human Immature Teeth

Kim

Shin

et al. 2016

Journal of Endodontics

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Carboxylesterase 1 (Ces1): from monocyte marker to major player

Cited by 21 publications

References 37 publications

Biosemantics guided gene expression profiling of Sjögren’s syndrome: a comparative analysis with systemic lupus erythematosus and rheumatoid arthritis

Biosemantics guided gene expression profiling of Sjögren’s syndrome: a comparative analysis with systemic lupus erythematosus and rheumatoid arthritis

Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Comparative Gene Expression Analysis of the Coronal Pulp and Apical Pulp Complex in Human Immature Teeth

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