DOCSLIB.ORG

Analysis and Update of the Human Aldehyde Dehydrogenase (ALDH

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Analysis and Update of the Human Aldehyde Dehydrogenase (ALDH UPDATE ON GENE COMPLETION AND ANNOTATIONS Analysis and update of the human aldehyde dehydrogenase ( ALDH)gene family Vasilis Vasiliou1*and Daniel W. Nebert 2 1 Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center,Denver, CO,USA 2 Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH, USA * Correspondence to:Tel: +1 303 315 6153; Fax: +1 303 315 6281; E-mail: [email protected] Date received: 23rd February2005 Abstract The aldehyde dehydrogenase ( ALDH)gene superfamily encodes enzymes that are critical for certain life processes and detoxification via the NAD(P)þ -dependent oxidation of numerous endogenous and exogenous aldehyde substrates, including pharmaceuticals and environmental pollutants. Analysis of the ALDH gene superfamily in the latest databases showed that the human genome contains 19 putativelyfunctional genes and three pseudogenes. Anumber of ALDH genes are upregulated as apart of the oxidative stress response and inexplicably overexpressed in various tumours, leading to problems during cancer chemotherapy. Mutations in ALDH genes cause inborn errors of metabolism —such as the Sjo¨ gren–Larsson syndrome,type II hyperprolinaemia and g -hydroxybutyric aciduria —and arelikely to contribute to several complex diseases, including cancer and Alzheimer’sdisease. The ALDH gene products appear to be multifunctional proteins, possessing both catalytic and non-catalytic properties. Keywords: human genome,aldehyde dehydrogenase gene family,genetic polymorphism, evolution, crystallins Introduction There are instances, however, in which ALDHscatalyse reactions yielding chemically reactive or bioactivemetabolites Aldehyde dehydrogenases (ALDHs; EC1.2.1.3) represent that are essential to the organism. Several ALDH enzymes — agroup of enzymes that oxidise awide range of endogenous including ALDH1A1, ALDH1A2 and ALDH1A3 —catalyse and exogenous aldehydes to their corresponding carboxylic the irreversible oxidationofretinal to retinoic acid.3 Whereas 1 acids. Endogenous aldehydes areformed during the meta- the light-absorbing properties of retinal are anecessary bolism of aminoacids, carbohydrates, lipids, biogenic amines, element for vision, thecarboxylic acid isomers, all-trans- vitamins and steroids. Biotransformations of alarge number of retinoic acid and/or 9-cis-retinoic acid, serve as ligands for the drugsand environmental chemicals also generate aldehydes. retinoic receptor (RAR)and the retinoid Xreceptor (RXR) Aldehydes arehighly reactiveelectrophilic compounds which that mediate geneexpression for growth and development.4 interactwiththiol and aminogroups, the resulting effects vary The importance of ALDH enzymes in retinoic acid formation from physiological and therapeutic to cytotoxic,mutagenic became evident from the fact that homozygous disruptionof or carcinogenic.Inthis respect, ALDHsefficiently oxidise and, the mouse Aldh1a2 gene results in an embryoniclethal in most instances, detoxify asignificantnumber of chemically phenotype due to defects in early heart morphogenesis,5,6 diverse aldehydes which otherwise would be harmful to the whereas Aldh1a3 null mice die shortly after birth, due to organism.Strong evidence supporting this notioncomes from respiratorydistress caused by choanal atresia.7 the fact that mutations in ALDH genes cause inbornerrorsof Formation of retinoic acid and g -aminobutyric acid metabolism associated with clinical phenotypes —such as (GABA) areamong the most intriguing functions of ALDHs Sjo¨ gren–Larssonsyndrome (SLS), type II hyperprolinaemia regarding bioactivation.GABA is implicated in theregulation 2 and g -hydroxybutyric aciduria. In addition, mutations in of the GABAergic,dopaminergic and opioid systems. Even ALDH genes contribute to clinically relevant diseases such as though the main pathway for GABA synthesis is the decar- cancer and Alzheimer’sdisease. boxylationof L -glutamate,this neurotransmitter can also be 138 q HENRYSTEWART PUBLICATIONS 1479–7364. HUMANGENOMICS .VOL 2. NO 2. 138–143 JUNE 2005 Analysis and update of the ALDH gene family UPDATE ON GENE COMPLETION AND ANNOTReviewATIONS formed from putrescine by directoxidativedeamination to balance. 12 Forexample,ithas been proposedthat ALDH3A1 give g -aminobutyraldehyde,which is then converted into mayscavenge hydroxyl radicals via the–SH groupsofCys and GABA by an ALDH. 8 Allinall, the ALDH gene family Met residues, and that both ALDH3A1 and ALDH1A1 may represents atruly diverse group of proteinswhich arecritical contribute to theantioxidant capacity of the cell by generating to metabolism. NADPH and/or NADH. 13 The enzymatic activity of ALDH3A1 generatesNADPH, which is linked to the regeneration of reduced glutathione (GSH) from its oxidised Multiple function(s) of the ALDH form(GSSG) via the glutathione reductase/peroxidase system. enzymes NAD(P)Hmay also function as adirect antioxidantby reducing glutathiyl radicals (GSz )ortyrosyl radicals.14 The Although the major function of ALDH enzymes is the expression of ALDH3A1 and ALDH1A1 at very high con- NAD(P)þ -dependentaldehyde oxidation, it has become centrations in the mammalian cornea and lens (crystallins) has increasingly clear that some, if not most, ALDHs exhibit led to additional hypothesesregarding the multifunctional multiple functions (Figure 1). For example,ALDH1A1, properties of these proteins —including astructural function ALDH2, ALDH3A1 and ALDH4A1 areknown to catalyse contributing to transparency. 15,16 Finally,the ALDH7A1 ester hydrolysis, suggestingthat the ALDHs mayhavemore gene product is similar to thegreen garden pea ‘26g protein’ than one catalytic function.9 Indeed, it has recently been involved in the regulation of turgor pressure, suggesting suggested that ALDH2 also possesses nitrate reductase activity, that the ALDH7A1 protein mighthaveosmoregulatory which catalyses the formation of 1,2-glyceryl dinitrate and properties. nitrite from nitroglycerin within mitochondria, leading to the production of cGMP and vasorelaxation.10 Aside from their catalytic properties,ALDH proteinsare Evolution of the ALDH genes capable of non-catalytic interactions with chemically diverse endogenous compounds and chemotherapeutic agents. In this ALDHshaveawide distribution in nature,ranging from context,ALDH1A1 has been identifiedasanandrogen- bacteria and yeaststoplants and animals.17 Sequence binding protein prominently expressed in humangenital comparisons indicate extensivesimilarity between bacterial fibroblasts; as acholesterol-binding protein in bovine lens and human ALDHs and suggest that the superfamily has a epithelium; and as acytosolic thyroid hormone-binding common ancestral gene,datingback to , 3billion yearsago. 18 protein in Xenopus . 11 ALDH1A1 has also been identifiedasa Asystematic nomenclatureschemefor the ALDH gene flavopyridol-binding protein in non-small cell lung carcinomas superfamily (in animals, plants, bacteria and yeasts) has been and as adaunorubicinbinding protein in rat liver. 1 Similar to developed, based on evolutionary divergence, 18 which has ALDH1A1, ALDH2 also displaysbinding capabilities with been implemented with biannual updates 19,20 and is available exogenous compounds, which became evident from its via the internet (http://www.aldh.org). identification as an acetaminophen binding protein. 1 ALDH proteins are conveniently classified into families and In addition, it has been suggested that someALDHsmay subfamilies based on the percentage of amino acid identity. playacritical role in cellular homeostasis by maintaining redox Proteinssharing $ 40 per cent identity areassigned to a particular family designated by an Arabic numeral, whereas those sharing $ 60 per cent identityare classified in the same • Aldehyde oxidation subfamily designated by aletter.These cut-off values follow • Catalytic • Ester hydrolysis the originalrecommendations by Margaret Dayhoff and 21 • Nitrate reductase were first applied to the cytochrome P-450 superfamily. At present, more than 130 additional gene superfamilies and • Endobiotics • Binding • Xenobiotics large gene families followthis same format. Functions of • Direct (GSH-like) • Antioxidant ALDHs • Indirect [generating NAD(P)H] Endogenous functions of ALDHs Antioxidants and oxidativestress increase the expression of • Structural • Cornea and lens crystallins certain ALDH genes, leading to increased protection of the cell against insult by environmental chemicals and drugs.22 • Regulatory • Osmotic pressure Increased expression of certain ALDHs in tumour cells, Figure 1. Multiple functions of aldehyde dehydrogenase however, leads to decreased cellular sensitivity to cyclopho- (ALDH) enzymes. Endobiotics, endogenous compounds. sphamide and other oxazaphosphorines and,thus, to clinical 23 Xenobiotics, foreign chemicals. problems in the treatment of cancer patients. The reason for certain ALDHs —and other non-P450 membersofthe [ Ah ] q HENRYSTEWART PUBLICATIONS 1479–7364. HUMANGENOMICS .VOL 2. NO 2. 138–143 JUNE 2005 139 UPDATERevieONw GENE COMPLETION AND ANNOTATIONS Vasiliou and Nebert battery—to be upregulated in some tumours24 remains dehydrogenase the number EC 1.2.1.31 —meaning that it an enigma. is closely related functionally to the other ALDH activities Numerous polymorphisms exist in the human ALDH (EC 1.2.1.3). genes, some of which cause inbornerrorsofmetabolism and The twomost recently discovered ALDH genes are
Load more

Recommended publications
  • (ALDH1A3) for the Maintenance of Non-Small Cell Lung Cancer Stem Cells Is Associated with the STAT3 Pathway
    Author Manuscript Published OnlineFirst on June 6, 2014; DOI: 10.1158/1078-0432.CCR-13-3292 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Essential role of aldehyde dehydrogenase 1A3 (ALDH1A3) for the maintenance of non-small cell lung cancer stem cells is associated with the STAT3 pathway Chunli Shao1,2, James P. Sullivan3, Luc Girard1,2, Alexander Augustyn1,2, Paul Yenerall1,2, Jaime Rodriguez4, Hui Liu4, Carmen Behrens4, Jerry W. Shay5, Ignacio I. Wistuba4, John D. Minna 1,2,6,7 1Hamon Center for Therapeutic Oncology Research, 2Simmons Comprehensive Cancer Center, 3Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, 02114, 4Department of Translational Molecular Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77054, 5Department of Cell Biology, 6Department of Pharmacology, 7Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, 75390, USA. Running Title: ALDH1A3 in non-small cell lung cancer stem cells Keywords: Lung cancer, cancer stem cells, ALDH1A3, STAT3, Stattic Financial Support This project was supported by CPRIT, NCI SPORE P50CA70907, UTSW Cancer Center Support Grant 5P30-CA142543, and the Gillson-Longenbaugh Foundation. Address Correspondence: John D. Minna, M.D. 6000 Harry Hines Blvd Dallas, TX 75390-8593 Hamon Center for Therapeutic Oncology Research UT Southwestern Medical Center Phone: 214-648-4900; Fax: 214-648-4940 [email protected] Disclosure of Potential Conflict of Interest The authors indicate no potential conflicts of interest. Word count: 4583 Total number of figures and tables: 6 figures Downloaded from clincancerres.aacrjournals.org on September 28, 2021. © 2014 American Association for Cancer Research.
    [Show full text]
  • The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance Over ALDH2*1 in Transduced Hela Cells
    The aldehyde dehydrogenase ALDH2*2 allele exhibits dominance over ALDH2*1 in transduced HeLa cells. Q Xiao, … , T Johnston, D W Crabb J Clin Invest. 1995;96(5):2180-2186. https://doi.org/10.1172/JCI118272. Research Article Individuals heterozygous or homozygous for the variant aldehyde dehydrogenase (ALDH2) allele (ALDH2*2), which encodes a protein differing only at residue 487 from the normal protein, have decreased ALDH2 activity in liver extracts and experience cutaneous flushing when they drink alcohol. The mechanisms by which this allele exerts its dominant effect is unknown. To study this effect, the human ALDH2*1 cDNA was cloned and the ALDH2*2 allele was generated by site-directed mutagenesis. These cDNAs were transduced using retroviral vectors into HeLa and CV1 cells, which do not express ALDH2. The normal allele directed synthesis of immunoreactive ALDH2 protein (ALDH2E) with the expected isoelectric point. Extracts of these cells contained increased aldehyde dehydrogenase activity with low Km for the aldehyde substrate. The ALDH2*2 allele directed synthesis of mRNA and immunoreactive protein (ALDH2K), but the protein lacked enzymatic activity. When ALDH2*1-expressing cells were transduced with ALDH2*2 vectors, both mRNAs were expressed and immunoreactive proteins with isoelectric points ranging between those of ALDH2E and ALDH2K were present, indicating that the subunits formed heteromers. ALDH2 activity in these cells was reduced below that of the parental ALDH2*1-expressing cells. Thus, the ALDH2*2 allele is sufficient to cause ALDH2 deficiency in vitro. Find the latest version: https://jci.me/118272/pdf The Aldehyde Dehydrogenase ALDH2*2 Allele Exhibits Dominance over ALDH2*1 in Transduced HeLa Cells Qing Xiao, * Henry Weiner,* Timothy Johnston,* and David W.
    [Show full text]
  • The Utility of Genetic Risk Scores in Predicting the Onset of Stroke March 2021 6
    DOT/FAA/AM-21/24 Office of Aerospace Medicine Washington, DC 20591 The Utility of Genetic Risk Scores in Predicting the Onset of Stroke Diana Judith Monroy Rios, M.D1 and Scott J. Nicholson, Ph.D.2 1. KR 30 # 45-03 University Campus, Building 471, 5th Floor, Office 510 Bogotá D.C. Colombia 2. FAA Civil Aerospace Medical Institute, 6500 S. MacArthur Blvd Rm. 354, Oklahoma City, OK 73125 March 2021 NOTICE This document is disseminated under the sponsorship of the U.S. Department of Transportation in the interest of information exchange. The United States Government assumes no liability for the contents thereof. _________________ This publication and all Office of Aerospace Medicine technical reports are available in full-text from the Civil Aerospace Medical Institute’s publications Web site: (www.faa.gov/go/oamtechreports) Technical Report Documentation Page 1. Report No. 2. Government Accession No. 3. Recipient's Catalog No. DOT/FAA/AM-21/24 4. Title and Subtitle 5. Report Date March 2021 The Utility of Genetic Risk Scores in Predicting the Onset of Stroke 6. Performing Organization Code 7. Author(s) 8. Performing Organization Report No. Diana Judith Monroy Rios M.D1, and Scott J. Nicholson, Ph.D.2 9. Performing Organization Name and Address 10. Work Unit No. (TRAIS) 1 KR 30 # 45-03 University Campus, Building 471, 5th Floor, Office 510, Bogotá D.C. Colombia 11. Contract or Grant No. 2 FAA Civil Aerospace Medical Institute, 6500 S. MacArthur Blvd Rm. 354, Oklahoma City, OK 73125 12. Sponsoring Agency name and Address 13. Type of Report and Period Covered Office of Aerospace Medicine Federal Aviation Administration 800 Independence Ave., S.W.
    [Show full text]
  • ATAP00021-Recombinant Human ALDH1A1 Protein
    ATAGENIX LABORATORIES Catalog Number:ATAP00021 Recombinant Human ALDH1A1 protein Product Details Summary English name Recombinant Human ALDH1A1 protein Purity >90% as determined by SDS-PAGE Endotoxin level Please contact with the lab for this information. Construction A DNA sequence encoding the human ALDH1A1 (Met1-Ser501) was fused with His tag Accession # P00352 Host E.coli Species Homo sapiens (Human) Predicted Molecular Mass 52.58 kDa Formulation Supplied as solution form in PBS pH 7.5 or lyophilized from PBS pH 7.5. Shipping In general, proteins are provided as lyophilized powder/frozen liquid. They are shipped out with dry ice/blue ice unless customers require otherwise. Stability &Storage Use a manual defrost freezer and avoid repeated freeze thaw cycles. Store at 2 to 8 °C for one week . Store at -20 to -80 °C for twelve months from the date of receipt. Reconstitution Reconstitute in sterile water for a stock solution.A copy of datasheet will be provided with the products, please refer to it for details. Background Background Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), also known as Aldehyde dehydrogenase 1 (ALDH1), or Retinaldehyde Dehydrogenase 1 (RALDH1), is an enzyme that is expressed at high levels in stem cells and that has been suggested to regulate stem cell function. The retinaldehyde dehydrogenase (RALDH) subfamily of ALDHs, composed of ALDH1A1, ALDH1A2, ALDH1A3, and ALDH8A1, regulate development by catalyzing retinoic acid biosynthesis. The ALDH1A1 protein belongs to the aldehyde dehydrogenases family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. ALDH1A1 also belongs to the group of corneal crystallins that Web:www.atagenix.com E-mail: [email protected] Tel: 027-87433958 ATAGENIX LABORATORIES Catalog Number:ATAP00021 Recombinant Human ALDH1A1 protein help maintain the transparency of the cornea.
    [Show full text]
  • PGENETICS-D-11-00413 Title: Integrating
    Editorial Manager(tm) for PLoS Genetics Manuscript Draft Manuscript Number: PGENETICS-D-11-00413 Title: Integrating genetic and gene expression evidence into genome-wide association analysis of gene sets Short Title: Integrative association analysis of gene sets Article Type: Research Article Section/Category: Natural Variation Keywords: gene set analysis; eQTL; integrative genomics Corresponding Author: Sayan Mukherjee Corresponding Author's Institution: Duke University First Author: Qing Xiong Order of Authors: Qing Xiong;Nicola Ancona;Elizabeth Hauser;Sayan Mukherjee;Terrence Furey Abstract: Background: Single variant or single gene analyses generally account for only a small proportion of the phenotypic variation in complex traits. Alternatively, gene set or pathway association analyses are playing an increasingly important role in uncovering genetic architectures of complex traits through the identification of systematic genetic interactions. Two dominant paradigms for gene set analyses are association analyses based on SNP genotypes and those based on gene expression profiles. However, gene-disease association can manifest in many ways such as alterations of gene expression, genotype and copy number, thus an integrative approach combining multiple forms of evidence can more accurately and comprehensively capture pathway associations. Methodology: We have developed a single statistical framework, Gene Set Association Analysis (GSAA), that simultaneously measures genome-wide patterns of genetic variation and gene expression variation
    [Show full text]
  • Transcriptomic Characterization of Fibrolamellar Hepatocellular
    Transcriptomic characterization of fibrolamellar PNAS PLUS hepatocellular carcinoma Elana P. Simona, Catherine A. Freijeb, Benjamin A. Farbera,c, Gadi Lalazara, David G. Darcya,c, Joshua N. Honeymana,c, Rachel Chiaroni-Clarkea, Brian D. Dilld, Henrik Molinad, Umesh K. Bhanote, Michael P. La Quagliac, Brad R. Rosenbergb,f, and Sanford M. Simona,1 aLaboratory of Cellular Biophysics, The Rockefeller University, New York, NY 10065; bPresidential Fellows Laboratory, The Rockefeller University, New York, NY 10065; cDivision of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; dProteomics Resource Center, The Rockefeller University, New York, NY 10065; ePathology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and fJohn C. Whitehead Presidential Fellows Program, The Rockefeller University, New York, NY 10065 Edited by Susan S. Taylor, University of California, San Diego, La Jolla, CA, and approved September 22, 2015 (received for review December 29, 2014) Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a exon of DNAJB1 and all but the first exon of PRKACA. This deletion of ∼400 kb in chromosome 19, resulting in a fusion of the produced a chimeric RNA transcript and a translated chimeric genes for the heat shock protein, DNAJ (Hsp40) homolog, subfam- protein that retains the full catalytic activity of wild-type PKA. ily B, member 1, DNAJB1, and the catalytic subunit of protein ki- This chimeric protein was found in 15 of 15 FLHCC patients nase A, PRKACA. The resulting chimeric transcript produces a (21) in the absence of any other recurrent mutations in the DNA fusion protein that retains kinase activity.
    [Show full text]
  • Location Analysis of Estrogen Receptor Target Promoters Reveals That
    Location analysis of estrogen receptor ␣ target promoters reveals that FOXA1 defines a domain of the estrogen response Jose´ e Laganie` re*†, Genevie` ve Deblois*, Ce´ line Lefebvre*, Alain R. Bataille‡, Franc¸ois Robert‡, and Vincent Gigue` re*†§ *Molecular Oncology Group, Departments of Medicine and Oncology, McGill University Health Centre, Montreal, QC, Canada H3A 1A1; †Department of Biochemistry, McGill University, Montreal, QC, Canada H3G 1Y6; and ‡Laboratory of Chromatin and Genomic Expression, Institut de Recherches Cliniques de Montre´al, Montreal, QC, Canada H2W 1R7 Communicated by Ronald M. Evans, The Salk Institute for Biological Studies, La Jolla, CA, July 1, 2005 (received for review June 3, 2005) Nuclear receptors can activate diverse biological pathways within general absence of large scale functional data linking these putative a target cell in response to their cognate ligands, but how this binding sites with gene expression in specific cell types. compartmentalization is achieved at the level of gene regulation is Recently, chromatin immunoprecipitation (ChIP) has been used poorly understood. We used a genome-wide analysis of promoter in combination with promoter or genomic DNA microarrays to occupancy by the estrogen receptor ␣ (ER␣) in MCF-7 cells to identify loci recognized by transcription factors in a genome-wide investigate the molecular mechanisms underlying the action of manner in mammalian cells (20–24). This technology, termed 17␤-estradiol (E2) in controlling the growth of breast cancer cells. ChIP-on-chip or location analysis, can therefore be used to deter- We identified 153 promoters bound by ER␣ in the presence of E2. mine the global gene expression program that characterize the Motif-finding algorithms demonstrated that the estrogen re- action of a nuclear receptor in response to its natural ligand.
    [Show full text]
  • Upregulation of ALDH1B1 Promotes Tumor Progression in Osteosarcoma
    www.impactjournals.com/oncotarget/ Oncotarget, 2018, Vol. 9, (No. 2), pp: 2502-2514 Research Paper Upregulation of ALDH1B1 promotes tumor progression in osteosarcoma Xin Wang1,*, Yan Yu2,*, Yuting He2,*, Qiqing Cai1, Songtao Gao1, Weitao Yao1, Zhiyong Liu1, Zhichao Tian1, Qicai Han3, Weiwei Wang4, Ranran Sun2, Yonggang Luo3 and Chao Li1 1Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China 2Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 3Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China 4Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China *These authors have contributed equally to this work Correspondence to: Chao Li, email: [email protected] Yonggang Luo, email: [email protected] Keywords: osteosarcoma; ALDH1B1; progression; proliferation; metastasis Received: August 21, 2017 Accepted: December 04, 2017 Published: December 20, 2017 Copyright: Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS.
    [Show full text]
  • Volatile and Intravenous Anesthesia Alter Rat Liver Proteins: Proteomic Time Course Analysis of Rat Liver Proteins
    8 The Open Proteomics Journal, 2012, 5, 8-16 Open Access Volatile and Intravenous Anesthesia Alter Rat Liver Proteins: Proteomic Time Course Analysis of Rat Liver Proteins Hisashi Watanabe1,*, Chihiro Kamagata2, Yoshiaki Tsuboko2 and Atsuhiro Sakamoto3 1Graduate Student, Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan 2Staff Member, Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan 3Professor and Chair, Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Abstract: Background: Our previous microarray study showed that sevoflurane anesthesia affects the expression of rat genes in multiple organs including the liver. In this study, we investigated whether liver protein expression was altered after propofol, sevoflurane, or isoflurane anesthesia. We also investigated differences in the time course of each drug 24 and 72 h after anesthesia. Methods: Rats were randomly assigned to four groups (non-anesthetized group and three groups anesthetized at each time point, n = 6 per group). A venous catheter was inserted into the caudal vein of all rats. Rats were anesthetized with each agent for 6 h, and the liver was obtained immediately after anesthesia. Proteomic analysis was performed. Results: About 4200 spots in each gel were discriminated, and at least 2619 spots were matched. Using LC-MS/MS, we identified 47 spots for propofol, 45 spots for sevoflurane, and 21 spots for isoflurane that were differentially expressed (p < 0.05) 0 h after anesthesia. The numbers of altered proteins were 14 and 19 in the isoflurane and sevoflurane groups, respectively, 72 h after anesthesia, but alterations in 40 proteins were seen in the propofol group 72 h after anesthesia.
    [Show full text]
  • Supplementary Materials
    1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No.
    [Show full text]
  • Identify Distinct Prognostic Impact of ALDH1 Family Members by TCGA Database in Acute Myeloid Leukemia
    Open Access Annals of Hematology & Oncology Research Article Identify Distinct Prognostic Impact of ALDH1 Family Members by TCGA Database in Acute Myeloid Leukemia Yi H, Deng R, Fan F, Sun H, He G, Lai S and Su Y* Department of Hematology, General Hospital of Chengdu Abstract Military Region, China Background: Acute myeloid leukemia is a heterogeneous disease. Identify *Corresponding author: Su Y, Department of the prognostic biomarker is important to guide stratification and therapeutic Hematology, General Hospital of Chengdu Military strategies. Region, Chengdu, 610083, China Method: We detected the expression level and the prognostic impact of Received: November 25, 2017; Accepted: January 18, each ALDH1 family members in AML by The Cancer Genome Atlas (TCGA) 2018; Published: February 06, 2018 database. Results: Upon 168 patients whose expression level of ALDH1 family members were available. We found that the level of ALDH1A1correlated to the prognosis of AML by the National Comprehensive Cancer Network (NCCN) stratification but not in other ALDH1 members. Moreover, we got survival data from 160 AML patients in TCGA database. We found that high ALDH1A1 expression correlated to poor Overall Survival (OS), mostly in Fms-like Tyrosine Kinase-3 (FLT3) mutated group. HighALDH1A2 expression significantly correlated to poor OS in FLT3 wild type population but not in FLT3 mutated group. High ALDH1A3 expression significantly correlated to poor OS in FLT3 mutated group but not in FLT3 wild type group. There was no relationship between the OS of AML with the level of ALDH1B1, ALDH1L1 and ALDH1L2. Conclusion: The prognostic impacts were different in each ALDH1 family members, which needs further investigation.
    [Show full text]
  • Mapping Aldehyde Dehydrogenase 1A1 Activity Using an [18F]Substrate-Based Approach Raul Pereira,[A] Thibault Gendron,[B] Chandan Sanghera,[A] Hannah E
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Birkbeck Institutional Research Online DOI: 10.1002/chem.201805473 Full Paper & Biochemistry Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18F]Substrate-Based Approach Raul Pereira,[a] Thibault Gendron,[b] Chandan Sanghera,[a] Hannah E. Greenwood,[a] Joseph Newcombe,[b, c] Patrick N. McCormick,[a] Kerstin Sander,[b] Maya Topf,[c] Erik rstad,[b] and Timothy H. Witney*[a] Abstract: Aldehyde dehydrogenases (ALDHs) catalyze the focused library of compounds evaluated, N-ethyl-6-(fluoro)- oxidation of aldehydes to carboxylic acids. Elevated ALDH N-(4-formylbenzyl)nicotinamide 4b was found to have excel- expression in human cancers is linked to metastases and lent affinity and isozyme selectivity for ALDH1A1 in vitro. poor overall survival. Despite ALDH being a poor prognostic Following 18F-fluorination, [18F]4b was taken up by colorectal factor, the non-invasive assessment of ALDH activity in vivo tumor cells and trapped through the conversion to its 18F-la- has not been possible due to a lack of sensitive and transla- beled carboxylate product under the action of ALDH. In vivo tional imaging agents. Presented in this report are the syn- positron emission tomography revealed high uptake of thesis and biological evaluation of ALDH1A1-selective chemi- [18F]4b in the lungs and liver, with radioactivity cleared cal probes composed of an aromatic aldehyde derived from through the urinary tract. Oxidation of [18F]4b, however, was N,N-diethylamino benzaldehyde (DEAB) linked to a fluorinat- observed in vivo, which may limit the tissue penetration of ed pyridine ring either via an amide or amine linkage.
    [Show full text]