Carboxylesterase 1 Plays an Essential Role in Non
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Proteomic Analyses Reveal a Role of Cytoplasmic Droplets As an Energy Source During Sperm Epididymal Maturation
Proteomic analyses reveal a role of cytoplasmic droplets as an energy source during sperm epididymal maturation Shuiqiao Yuana,b, Huili Zhenga, Zhihong Zhengb, Wei Yana,1 aDepartment of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, 89557; and bDepartment of Laboratory Animal Medicine, China Medical University, Shenyang, 110001, China Corresponding author. Email: [email protected] Supplemental Information contains one Figure (Figure S1), three Tables (Tables S1-S3) and two Videos (Videos S1 and S2) files. Figure S1. Scanning electron microscopic images of purified murine cytoplasmic droplets. Arrows point to indentations resembling the resealed defects at the detaching points when CDs come off the sperm flagella. Scale bar = 1µm Table S1 Mass spectrometry-based identifiaction of proteins highly enriched in murine cytoplasmic droplets. # MS/MS View:Identified Proteins (105) Accession Number Molecular Weight Protein Grouping Ambiguity Dot_1_1 Dot_2_1 Dot_3_1 Dot_4_1Dot_5_1 Dot_1_2 Dot_2_2 Dot_3_2 Dot_4_2 Dot_5_2 1 IPI:IPI00467457.3 Tax_Id=10090 Gene_Symbol=Ldhc L-lactate dehydrogenase C chain IPI00467457 36 kDa TRUE 91% 100% 100% 100% 100% 100% 100% 100% 100% 2 IPI:IPI00473320.2 Tax_Id=10090 Gene_Symbol=Actb Putative uncharacterized protein IPI00473320 42 kDa TRUE 75% 100% 100% 100% 100% 89% 76% 100% 100% 100% 3 IPI:IPI00224181.7 Tax_Id=10090 Gene_Symbol=Akr1b7 Aldose reductase-related protein 1 IPI00224181 36 kDa TRUE 100% 100% 76% 100% 100% 4 IPI:IPI00228633.7 Tax_Id=10090 Gene_Symbol=Gpi1 Glucose-6-phosphate -
1 Metabolic Dysfunction Is Restricted to the Sciatic Nerve in Experimental
Page 1 of 255 Diabetes Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy Oliver J. Freeman1,2, Richard D. Unwin2,3, Andrew W. Dowsey2,3, Paul Begley2,3, Sumia Ali1, Katherine A. Hollywood2,3, Nitin Rustogi2,3, Rasmus S. Petersen1, Warwick B. Dunn2,3†, Garth J.S. Cooper2,3,4,5* & Natalie J. Gardiner1* 1 Faculty of Life Sciences, University of Manchester, UK 2 Centre for Advanced Discovery and Experimental Therapeutics (CADET), Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK 3 Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK 4 School of Biological Sciences, University of Auckland, New Zealand 5 Department of Pharmacology, Medical Sciences Division, University of Oxford, UK † Present address: School of Biosciences, University of Birmingham, UK *Joint corresponding authors: Natalie J. Gardiner and Garth J.S. Cooper Email: [email protected]; [email protected] Address: University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, United Kingdom Telephone: +44 161 275 5768; +44 161 701 0240 Word count: 4,490 Number of tables: 1, Number of figures: 6 Running title: Metabolic dysfunction in diabetic neuropathy 1 Diabetes Publish Ahead of Print, published online October 15, 2015 Diabetes Page 2 of 255 Abstract High glucose levels in the peripheral nervous system (PNS) have been implicated in the pathogenesis of diabetic neuropathy (DN). However our understanding of the molecular mechanisms which cause the marked distal pathology is incomplete. Here we performed a comprehensive, system-wide analysis of the PNS of a rodent model of DN. -
Carboxylesterase 1 / CES1 Antibody (Internal) Goat Polyclonal Antibody Catalog # ALS12250
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 Carboxylesterase 1 / CES1 Antibody (Internal) Goat Polyclonal Antibody Catalog # ALS12250 Specification Carboxylesterase 1 / CES1 Antibody (Internal) - Product Information Application WB, IHC Primary Accession P23141 Reactivity Human Host Goat Clonality Polyclonal Calculated MW 63kDa KDa Carboxylesterase 1 / CES1 Antibody (Internal) - Additional Information Gene ID 1066 Antibody (0.03 ug/ml) staining of Human Liver lysate (35 ug protein in RIPA buffer). Other Names Liver carboxylesterase 1, Acyl-coenzyme A:cholesterol acyltransferase, ACAT, Brain carboxylesterase hBr1, Carboxylesterase 1, CE-1, hCE-1, 3.1.1.1, Cocaine carboxylesterase, Egasyn, HMSE, Methylumbelliferyl-acetate deacetylase 1, 3.1.1.56, Monocyte/macrophage serine esterase, Retinyl ester hydrolase, REH, Serine esterase 1, Triacylglycerol hydrolase, TGH, CES1, CES2, SES1 Target/Specificity Human CES1. This antibody is expected to recognise all three reported isoforms (NP_001020366.1; NP_001020365.1; Anti-CES1 antibody IHC of human lung. NP_001257.4). Reconstitution & Storage Carboxylesterase 1 / CES1 Antibody Store at -20°C. Minimize freezing and (Internal) - Background thawing. Involved in the detoxification of xenobiotics Precautions and in the activation of ester and amide Carboxylesterase 1 / CES1 Antibody prodrugs. Hydrolyzes aromatic and aliphatic (Internal) is for research use only and not esters, but has no catalytic activity toward for use in diagnostic or therapeutic amides or a fatty acyl-CoA ester. Hydrolyzes procedures. the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form Carboxylesterase 1 / CES1 Antibody (Internal) - cocaethylene. Displays fatty acid ethyl ester Protein Information synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Current Drug Metabolism, 2019, 20, 91-102
Send Orders for Reprints to [email protected] 91 Current Drug Metabolism, 2019, 20, 91-102 REVIEW ARTICLE ISSN: 1389-2002 eISSN: 1875-5453 Current Drug Impact Factor: Metabolism 2.655 The Impact of Carboxylesterases in Drug Metabolism and Pharmacokinetics The international journal for timely in-depth reviews on Drug Metabolism BENTHAM SCIENCE Li Di* Pfizer Inc., Eastern Point Road, Groton, Connecticut, CT 06354, USA Abstract: Background: Carboxylesterases (CES) play a critical role in catalyzing hydrolysis of esters, amides, car- bamates and thioesters, as well as bioconverting prodrugs and soft drugs. The unique tissue distribution of CES en- zymes provides great opportunities to design prodrugs or soft drugs for tissue targeting. Marked species differences in CES tissue distribution and catalytic activity are particularly challenging in human translation. Methods: Review and summarization of CES fundamentals and applications in drug discovery and development. A R T I C L E H I S T O R Y Results: Human CES1 is one of the most highly expressed drug metabolizing enzymes in the liver, while human intestine only expresses CES2. CES enzymes have moderate to high inter-individual variability and exhibit low to no expression in the fetus, but increase substantially during the first few months of life. The CES genes are highly po- Received: June 04, 2018 Revised: August 03, 2018 lymorphic and some CES genetic variants show significant influence on metabolism and clinical outcome of certain Accepted: August 08, 2018 drugs. Monkeys appear to be more predictive of human pharmacokinetics for CES substrates than other species. Low risk of clinical drug-drug interaction is anticipated for CES, although they should not be overlooked, particularly DOI: 10.2174/1389200219666180821094502 interaction with alcohols. -
The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z
REVIEW pubs.acs.org/CR The Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease Jonathan Z. Long* and Benjamin F. Cravatt* The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States CONTENTS 2.4. Other Phospholipases 6034 1. Introduction 6023 2.4.1. LIPG (Endothelial Lipase) 6034 2. Small-Molecule Hydrolases 6023 2.4.2. PLA1A (Phosphatidylserine-Specific 2.1. Intracellular Neutral Lipases 6023 PLA1) 6035 2.1.1. LIPE (Hormone-Sensitive Lipase) 6024 2.4.3. LIPH and LIPI (Phosphatidic Acid-Specific 2.1.2. PNPLA2 (Adipose Triglyceride Lipase) 6024 PLA1R and β) 6035 2.1.3. MGLL (Monoacylglycerol Lipase) 6025 2.4.4. PLB1 (Phospholipase B) 6035 2.1.4. DAGLA and DAGLB (Diacylglycerol Lipase 2.4.5. DDHD1 and DDHD2 (DDHD Domain R and β) 6026 Containing 1 and 2) 6035 2.1.5. CES3 (Carboxylesterase 3) 6026 2.4.6. ABHD4 (Alpha/Beta Hydrolase Domain 2.1.6. AADACL1 (Arylacetamide Deacetylase-like 1) 6026 Containing 4) 6036 2.1.7. ABHD6 (Alpha/Beta Hydrolase Domain 2.5. Small-Molecule Amidases 6036 Containing 6) 6027 2.5.1. FAAH and FAAH2 (Fatty Acid Amide 2.1.8. ABHD12 (Alpha/Beta Hydrolase Domain Hydrolase and FAAH2) 6036 Containing 12) 6027 2.5.2. AFMID (Arylformamidase) 6037 2.2. Extracellular Neutral Lipases 6027 2.6. Acyl-CoA Hydrolases 6037 2.2.1. PNLIP (Pancreatic Lipase) 6028 2.6.1. FASN (Fatty Acid Synthase) 6037 2.2.2. PNLIPRP1 and PNLIPR2 (Pancreatic 2.6.2. -
Isolation and Characterization of the Prolyl Aminopeptidase Gene (Pap) from Aeromonas Sobria: Comparison with the Bacillus Coagulans Enzyme1
J. Biochem. 116, 818-825 (1994) Isolation and Characterization of the Prolyl Aminopeptidase Gene (pap) from Aeromonas sobria: Comparison with the Bacillus coagulans Enzyme1 Ana Kitazono,* Atsuko Kitano,* Daisuke Tsuru,•õ and Tadashi Yoshimoto*,2 *School of Pharmaceutical Sciences , Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki 852; and •õ Department of Applied Microbiology, Kumamoto Institute of Technology, 4-22-1 Ikeda, Kumamoto, Kumamoto 860 Received for publication, May 16, 1994 The Aeromonas sobria pap gene encoding prolyl aminopeptidase (PAP) was cloned. It consists of 425 codons and encodes a homotetrameric enzyme of 205kDa. The purified enzyme showed an almost absolute specificity for amino-terminal proline. Proline and hydroxyproline residues from many peptide and amide substrates could be easily removed, while no activity was detected for substrates having other amino terminals. The enzyme was very similar to that from Bacillus coagulans in many aspects, such as the strong inhibition caused by PCMB and the weak or no inhibition caused by DFP and chelators, respectively. However, these enzymes show only 15% identity in their amino acid sequences. Differences were also observed in their molecular weight, stability and activity toward some peptide substrates. When aligning the deduced amino acid sequence with known sequences from other microorganisms, conserved sequences were found at the amino-terminal region; the significance of these conserved regions is discussed. Based on the results of this work, and on the studies available to date, the occurrence of at least two types of PAPs is postulated. One group would be formed by the Bacillus, Neisseria, and Lactobacillus enzymes, and the other by enzymes such as the Aeromonas PAP. -
PDE6) by the Glutamic Acid- Rich Protein-2 (GARP2)
University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Fall 2013 Regulation of the catalytic and allosteric properties of photoreceptor phosphodiesterase (PDE6) by the glutamic acid- rich protein-2 (GARP2) Wei Yao Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation Yao, Wei, "Regulation of the catalytic and allosteric properties of photoreceptor phosphodiesterase (PDE6) by the glutamic acid-rich protein-2 (GARP2)" (2013). Doctoral Dissertations. 747. https://scholars.unh.edu/dissertation/747 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. REGULATION OF THE CATALYTIC AND ALLOSTERIC PROPERTIES OF PHOTORECEPTOR PHOSPHODIESTERASE (PDE6) BY THE GLUTAMIC ACID-RICH PROTEIN-2 (GARP2) BY WEI YAO B.S., Jinan University, 2007 DISSERTATION Submitted to the University of New Hampshire in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biochemistry September, 2013 UMI Number: 3575987 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Di!ss0?t&iori Piiblist’Mlg UMI 3575987 Published by ProQuest LLC 2013. Copyright in the Dissertation held by the Author. -
P-Glycoprotein, CYP3A, and Plasma Carboxylesterase Determine Brain and Blood Disposition of the Mtor Inhibitor Everolimus (Afinitor) in Mice
Published OnlineFirst April 11, 2014; DOI: 10.1158/1078-0432.CCR-13-1759 Clinical Cancer Cancer Therapy: Preclinical Research P-Glycoprotein, CYP3A, and Plasma Carboxylesterase Determine Brain and Blood Disposition of the mTOR Inhibitor Everolimus (Afinitor) in Mice Seng Chuan Tang1, Rolf W. Sparidans3, Ka Lei Cheung4, Tatsuki Fukami5, Selvi Durmus1, Els Wagenaar1, Tsuyoshi Yokoi5, Bart J.M. van Vlijmen4, Jos H. Beijnen2,3, and Alfred H. Schinkel1 Abstract Purpose: To clarify the role of ABCB1, ABCG2, and CYP3A in blood and brain exposure of everolimus using knockout mouse models. À À À À À À À À Experimental Design: We used wild-type, Abcb1a/1b / , Abcg2 / , Abcb1a/1b;Abcg2 / , and Cyp3a / mice to study everolimus oral bioavailability and brain accumulation. Results: Following everolimus administration, brain concentrations and brain-to-liver ratios were À À À À À À substantially increased in Abcb1a/1b / and Abcb1a/1b;Abcg2 / , but not Abcg2 / mice. The fraction of everolimus located in the plasma compartment was highly increased in all knockout strains. In vitro, everolimus was rapidly degraded in wild-type but not knockout plasma. Carboxylesterase 1c (Ces1c), a plasma carboxylesterase gene, was highly upregulated (80-fold) in the liver of knockout mice relative to wild-type mice, and plasma Ces1c likely protected everolimus from degradation by binding and stabilizing it. This binding was prevented by preincubation with the carboxylesterase inhibitor BNPP. In vivo knockdown experiments confirmed the involvement of Ces1c in everolimus stabilization. Everolimus also markedly inhibited the hydrolysis of irinotecan and p-nitrophenyl acetate by mouse plasma carboxylesterase À À and recombinant human CES2, respectively. -
Baboon JMP CES Paper
Baboon carboxylesterases 1 and 2: sequences, structures and phylogenetic relationships with human and other primate carboxylesterases Author Holmes, Roger S, Glenn, Jeremy P, VandeBerg, John L, Cox, Laura A Published 2009 Journal Title Journal of Medical Primatology DOI https://doi.org/10.1111/j.1600-0684.2008.00315.x Copyright Statement © 2009 John Wiley & Sons A/S. This is the author-manuscript version of the paper. Reproduced in accordance with the copyright policy of the publisher.The definitive version is available at www.interscience.wiley.com Downloaded from http://hdl.handle.net/10072/29362 Griffith Research Online https://research-repository.griffith.edu.au Baboon Carboxylesterases 1 and 2: Sequences, Structures and Phylogenetic Relationships with Human and other Primate Carboxylesterases Roger S. Holmes 1,2,3 , Jeremy P. Glenn 1, John L. VandeBerg 1,2 , Laura A. Cox 1,2,4 1. Department of Genetics and 2. Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, San Antonio, TX, USA, and 3. School of Biomolecular and Physical Sciences, Griffith University, Nathan. Queensland, Australia 4. Corresponding Author: Laura A. Cox, Ph.D. Department of Genetics Southwest National Primate Research Center Southwest Foundation for Biomedical Research San Antonio, TX, USA 78227 Email: [email protected] Phone: 210-258-9687 Fax: 210-258-9600 Keywords: cDNA sequence; amino acid sequence; 3-D structure Running Head: Carboxylesterases: sequences and phylogeny Published in Journal of Medical Primatology (2009) 38: 27-38. Abstract Background Carboxylesterase (CES) is predominantly responsible for the detoxification of a wide range of drugs and narcotics, and catalyze several reactions in cholesterol and fatty acid metabolism. -
Supplementary Table 3: Calcineurin- and Aging-Sensitive Genes
Supplementary Table 3: Calcineurin- and Aging-Sensitive Genes Supplementary Table 3: Calcineurin up/ Aging up (pages 1 -2)- genes classified as Ad-aCaN up in the present study (see Supplementary Table 1), as well as reported as significantly increased in our prior aging study (Blalock et al., 2003, see supplementary tables 3, 4 and 5). Calcineurin Down/ Aging Down (page 2), Calcineurin Up/ Aging Down (pages 2-3),and Calcineurin Down/Aging Up (page 3)as above except for direction of change. - Columns: Probe Set- Affymetrix probe set identifier for RG-U34A microarray, Symbol and Title- annotated information for above probe set (annotation downloaded June, 2004), Calcineurin ANOVA- p-value for 1-way Analysis of Variance. Calcineurin Up/Aging Up Probe set Symbol Title CaN ANOVA rc_AI170268_at B2m beta-2 microglobulin 0.00000 rc_AI102299_s_at Bid3 BH3 interacting domain 3 0.00721 X52477_at C3 complement component 3 0.00000 X58294_at Ca2 carbonic anhydrase 2 0.00004 X76489cds_g_at Cd9 CD9 antigen 0.00000 L07736_at Cpt1a carnitine palmitoyltransferase 1, liver 0.00001 M55534mRNA_s_at Cryab crystallin, alpha B 0.00000 X60351cds_s_at Cryab crystallin, alpha B 0.00000 rc_AI234146_at Csrp1 cysteine and glycine-rich protein 1 0.00000 rc_AI176595_s_at Ctsl cathepsin L 0.00001 D00569_at Decr1 2,4-dienoyl CoA reductase 1, mitochondrial 0.00000 rc_AA924925_at Dri42 ER transmembrane protein Dri 42 0.00000 rc_AA848831_at Edg2 endothelial differentiation, lysophosphatidic acid GPCR, 2 0.00000 X14323cds_g_at Fcgrt Fc receptor, IgG, alpha chain transporter -
Challenges on Cyclic Nucleotide Phosphodiesterases Imaging with Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights Since 2016
International Journal of Molecular Sciences Review Challenges on Cyclic Nucleotide Phosphodiesterases Imaging with Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights since 2016 Susann Schröder 1,2,* , Matthias Scheunemann 2, Barbara Wenzel 2 and Peter Brust 2 1 Department of Research and Development, ROTOP Pharmaka Ltd., 01328 Dresden, Germany 2 Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), 04318 Leipzig, Germany; [email protected] (M.S.); [email protected] (B.W.); [email protected] (P.B.) * Correspondence: [email protected]; Tel.: +49-341-234-179-4631 Abstract: Cyclic nucleotide phosphodiesterases (PDEs) represent one of the key targets in the research field of intracellular signaling related to the second messenger molecules cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP). Hence, non-invasive imaging of this enzyme class by positron emission tomography (PET) using appropriate isoform- selective PDE radioligands is gaining importance. This methodology enables the in vivo diagnosis and staging of numerous diseases associated with altered PDE density or activity in the periphery and the central nervous system as well as the translational evaluation of novel PDE inhibitors as therapeutics. In this follow-up review, we summarize the efforts in the development of novel PDE radioligands and highlight (pre-)clinical insights from PET studies using already known PDE Citation: Schröder, S.; Scheunemann, radioligands since 2016. M.; Wenzel, B.; Brust, P. Challenges on Cyclic Nucleotide Keywords: positron emission tomography; cyclic nucleotide phosphodiesterases; PDE inhibitors; Phosphodiesterases Imaging with PDE radioligands; radiochemistry; imaging; recent (pre-)clinical insights Positron Emission Tomography: Novel Radioligands and (Pre-)Clinical Insights since 2016.