A Missense Mutation in ALDH1A3 Causes Isolated Microphthalmia/Anophthalmia in Nine Individuals from an Inbred Muslim Kindred
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(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. -
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. -
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. -
Overall Survival of Pancreatic Ductal Adenocarcinoma Is Doubled by Aldh7a1 Deletion in the KPC Mouse
Overall survival of pancreatic ductal adenocarcinoma is doubled by Aldh7a1 deletion in the KPC mouse Jae-Seon Lee1,2*, Ho Lee3*, Sang Myung Woo4, Hyonchol Jang1, Yoon Jeon1, Hee Yeon Kim1, Jaewhan Song2, Woo Jin Lee4, Eun Kyung Hong5, Sang-Jae Park4, Sung- Sik Han4§§ and Soo-Youl Kim1§ 1Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Republic of Korea. 2Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea. 3Graduate School of Cancer Science and Policy, 4Department of Surgery, Center for Liver and Pancreatobiliary Cancer and 5Department of Pathology, National Cancer Center, Goyang, Republic of Korea. Correspondence §Corresponding author: [email protected] (S.-Y.K.) §§Co-corresponding author: [email protected] (S.-S.H.) *These authors contributed equally to this work 1 Abstract Rationale: The activity of aldehyde dehydrogenase 7A1 (ALDH7A1), an enzyme that catalyzes the lipid peroxidation of fatty aldehydes was found to be upregulated in pancreatic ductal adenocarcinoma (PDAC). ALDH7A1 knockdown significantly reduced tumor formation in PDAC. We raised a question how ALDH7A1 contributes to cancer progression. Methods: To answer the question, the role of ALDH7A1 in energy metabolism was investigated by knocking down and knockdown gene in mouse model, because the role of ALDH7A1 has been reported as a catabolic enzyme catalyzing fatty aldehyde from lipid peroxidation to fatty acid. Oxygen consumption rate (OCR), ATP production, mitochondrial membrane potential, proliferation assay and immunoblotting were performed. In in vivo study, two human PDAC cell lines were used for pre-clinical xenograft model as well as spontaneous PDAC model of KPC mice was also employed for anti-cancer therapeutic effect. -
Acquire a High Level of Retinoic Acid− Producing Capacity in Response to Vitamin D 3 This Information Is Current As of September 28, 2021
Human CD1c+ Myeloid Dendritic Cells Acquire a High Level of Retinoic Acid− Producing Capacity in Response to Vitamin D 3 This information is current as of September 28, 2021. Takayuki Sato, Toshio Kitawaki, Haruyuki Fujita, Makoto Iwata, Tomonori Iyoda, Kayo Inaba, Toshiaki Ohteki, Suguru Hasegawa, Kenji Kawada, Yoshiharu Sakai, Hiroki Ikeuchi, Hiroshi Nakase, Akira Niwa, Akifumi Takaori-Kondo and Norimitsu Kadowaki Downloaded from J Immunol 2013; 191:3152-3160; Prepublished online 21 August 2013; doi: 10.4049/jimmunol.1203517 http://www.jimmunol.org/content/191/6/3152 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2013/08/21/jimmunol.120351 Material 7.DC1 References This article cites 41 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/191/6/3152.full#ref-list-1 by guest on September 28, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. -
CHD7 Represses the Retinoic Acid Synthesis Enzyme ALDH1A3 During Inner Ear Development
CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development Hui Yao, … , Shigeki Iwase, Donna M. Martin JCI Insight. 2018;3(4):e97440. https://doi.org/10.1172/jci.insight.97440. Research Article Development Neuroscience CHD7, an ATP-dependent chromatin remodeler, is disrupted in CHARGE syndrome, an autosomal dominant disorder characterized by variably penetrant abnormalities in craniofacial, cardiac, and nervous system tissues. The inner ear is uniquely sensitive to CHD7 levels and is the most commonly affected organ in individuals with CHARGE. Interestingly, upregulation or downregulation of retinoic acid (RA) signaling during embryogenesis also leads to developmental defects similar to those in CHARGE syndrome, suggesting that CHD7 and RA may have common target genes or signaling pathways. Here, we tested three separate potential mechanisms for CHD7 and RA interaction: (a) direct binding of CHD7 with RA receptors, (b) regulation of CHD7 levels by RA, and (c) CHD7 binding and regulation of RA-related genes. We show that CHD7 directly regulates expression of Aldh1a3, the gene encoding the RA synthetic enzyme ALDH1A3 and that loss of Aldh1a3 partially rescues Chd7 mutant mouse inner ear defects. Together, these studies indicate that ALDH1A3 acts with CHD7 in a common genetic pathway to regulate inner ear development, providing insights into how CHD7 and RA regulate gene expression and morphogenesis in the developing embryo. Find the latest version: https://jci.me/97440/pdf RESEARCH ARTICLE CHD7 represses the retinoic acid synthesis enzyme ALDH1A3 during inner ear development Hui Yao,1 Sophie F. Hill,2 Jennifer M. Skidmore,1 Ethan D. Sperry,3,4 Donald L. -
ALDH2 Antibody (Center)
BioVision 05/14 For research use only ALDH2 Antibody (Center) ALTERNATE NAMES: ALDH2; ALDM; Aldehyde dehydrogenase, mitochondrial; ALDH class 2; ALDH-E2; ALDHI. CATALOG #: 6748-100 AMOUNT: 100 µl HOST/ISOTYPE: Rabbit IgG Western blot analysis in A549 cell lysates and mouse liver and lung and rat liver IMMUNOGEN: This ALDH2 antibody is generated from rabbits immunized with tissue lysates (35 µg/lane). a KLH conjugated synthetic peptide between 318-347 amino acids from the Central region of human ALDH2. PURIFICATION: This antibody is purified through a protein A column, followed by peptide affinity purification. MOLECULAR WEIGHT: ~56.38 kDa FORM: Liquid FORMULATION: Supplied in PBS with 0.09% (W/V) sodium azide. SPECIES REACTIVITY: Human. Predicted cross reactivity with mouse and rat samples. STORAGE CONDITIONS: Maintain refrigerated at 2-8°C for up to 6 months. For long term storage, store at -20°C in small aliquots to prevent freeze-thaw cycles. Formalin-fixed and paraffin-embedded human hepatocarcinoma reacted with ALDH2 antibody, DESCRIPTION: ALDH2 (Aldehyde dehydrogenase 2 family) belongs to the aldehyde which was peroxidase-conjugated to the dehydrogenase family which catalyze the chemical transformation from acetaldehyde to secondary antibody, followed by DAB staining. acetic acid and is the second enzyme of the major oxidative pathway of alcohol metabolism. Aldehyde dehydrogenases (ALDHs) mediate NADP+-dependent oxidation of aldehydes into acids during detoxification of alcohol-derived acetaldehyde; lipid peroxidation; and metabolism of corticosteroids, biogenic amines and neurotransmitters. ALDH1A1, also designated retinal dehydrogenase 1 (RalDH1 or RALDH1); aldehyde dehydrogenase family 1 member A1; aldehyde dehydrogenase cytosolic; ALDHII; ALDH-E1 or ALDH E1, is a retinal dehydrogenase that participates in the biosynthesis of retinoic acid (RA). -
Insights Into Aldehyde Dehydrogenase Enzymes: a Structural Perspective
REVIEW published: 14 May 2021 doi: 10.3389/fmolb.2021.659550 Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective Kim Shortall, Ahmed Djeghader, Edmond Magner and Tewfik Soulimane* Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland Aldehyde dehydrogenases engage in many cellular functions, however their dysfunction resulting in accumulation of their substrates can be cytotoxic. ALDHs are responsible for the NAD(P)-dependent oxidation of aldehydes to carboxylic acids, participating in detoxification, biosynthesis, antioxidant and regulatory functions. Severe diseases, including alcohol intolerance, cancer, cardiovascular and neurological diseases, were linked to dysfunctional ALDH enzymes, relating back to key enzyme structure. An in-depth understanding of the ALDH structure-function relationship and mechanism of action is key to the understanding of associated diseases. Principal structural features 1) cofactor binding domain, 2) active site and 3) oligomerization mechanism proved critical in maintaining ALDH normal activity. Emerging research based on the combination of structural, functional and biophysical studies of bacterial and eukaryotic ALDHs contributed to the appreciation of diversity within the superfamily. Herewith, we Edited by: discuss these studies and provide our interpretation for a global understanding of Ashley M Buckle, ALDH structure and its purpose–including correct function and role in disease. Our Monash University, Australia analysis provides a synopsis -
Severe Osteoarthritis of the Hand Associates with Common Variants Within the ALDH1A2 Gene and with Rare Variants at 1P31
Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Helgadottir, Hafdis T; Bomer, Nils; Metrustry, Sarah; Bierma-Zeinstra, S; Strijbosch, Annelieke M; Evangelou, Evangelos; Hart, Deborah; Beekman, Marian; Jonasdottir, Aslaug; Sigurdsson, Asgeir; Eiriksson, Finnur F; Thorsteinsdottir, Margret; Frigge, Michael L; Kong, Augustine; Gudjonsson, Sigurjon A; Magnusson, Olafur T; Masson, Gisli; Hofman, Albert; Arden, Nigel K; Ingvarsson, Thorvaldur; Lohmander, Stefan; Kloppenburg, Margreet; Rivadeneira, Fernando; Nelissen, Rob G H H; Spector, Tim; Uitterlinden, Andre; Slagboom, P Eline; Thorsteinsdottir, Unnur; Jonsdottir, Ingileif; Valdes, Ana M; Meulenbelt, Ingrid; van Meurs, Joyce; Jonsson, Helgi; Stefansson, Kari Published in: Nature Genetics DOI: 10.1038/ng.2957 2014 Link to publication Citation for published version (APA): Styrkarsdottir, U., Thorleifsson, G., Helgadottir, H. T., Bomer, N., Metrustry, S., Bierma-Zeinstra, S., Strijbosch, A. M., Evangelou, E., Hart, D., Beekman, M., Jonasdottir, A., Sigurdsson, A., Eiriksson, F. F., Thorsteinsdottir, M., Frigge, M. L., Kong, A., Gudjonsson, S. A., Magnusson, O. T., Masson, G., ... Stefansson, K. (2014). Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31. Nature Genetics, 46(5), 498-502. https://doi.org/10.1038/ng.2957 Total number of authors: 36 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. -
ALDH1A2 Is a Candidate Tumor Suppressor Gene in Ovarian Cancer
cancers Article ALDH1A2 Is a Candidate Tumor Suppressor Gene in Ovarian Cancer Jung-A Choi 1, Hyunja Kwon 1, Hanbyoul Cho 1,* , Joon-Yong Chung 2 , Stephen M. Hewitt 2 and Jae-Hoon Kim 1 1 Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Korea; [email protected] (J.-A.C.); [email protected] (H.K.); [email protected] (J.-H.K.) 2 Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] (J.-Y.C.); [email protected] (S.M.H.) * Correspondence: [email protected]; Tel.: +82-2-2019-3430; Fax: +82-2-3462-8209 Received: 11 July 2019; Accepted: 10 October 2019; Published: 14 October 2019 Abstract: Aldehyde dehydrogenase 1 family member A2 (ALDH1A2) is a rate-limiting enzyme involved in cellular retinoic acid synthesis. However, its functional role in ovarian cancer remains elusive. Here, we found that ALDH1A2 was the most prominently downregulated gene among ALDH family members in ovarian cancer cells, according to complementary DNA microarray data. Low ALDH1A2 expression was associated with unfavorable prognosis and shorter disease-free and overall survival for ovarian cancer patients. Notably, hypermethylation of ALDH1A2 was significantly higher in ovarian cancer cell lines when compared to that in immortalized human ovarian surface epithelial cell lines. ALDH1A2 expression was restored in various ovarian cancer cell lines after treatment with the DNA methylation inhibitor 5-aza-20-deoxycytidine. Furthermore, silencing DNA methyltransferase 1 (DNMT1) or 3B (DNMT3B) restored ALDH1A2 expression in ovarian cancer cell lines. -
Human Skeletal Muscle Satellite Cells Co-Express Aldehyde Dehydrogenase Isoforms Aldh1a1 & Aldh1a3
Research Article Journal of Volume 12:4, 2021 Cytology & Histology ISSN: 2157-7099 Open Access Human Skeletal Muscle Satellite Cells Co-Express Aldehyde Dehydrogenase Isoforms Aldh1A1 & Aldh1A3 Laura Sophie Rihani*, Friederike Liesche-Starnecker and Jürgen Schlegel Department of Neuropathology, Institute of Pathology, Technical University Munich, Germany Abstract Satellite cells (SC) constitute the stem cell population of skeletal muscle and conduct myogenic growth and differentiation. Recently, aldehyde dehydrogenase 1 (ALDH1) has been identified as a novel myogenic factor in experimental models of SCs. ALDH1 constitutes a subfamily of the ALDH enzyme super family. The enzymatic functions of ALDH1 isoforms include both protection against oxidative stress products and regulation of differentiation as pacemaker enzyme in retinoic acid signaling. Although ALDH enzymatic activity has been demonstrated in SCs it is not clear which isoforms are important in human skeletal muscle. Here, we show that ALDH1A1 and ALDH1A3 are expressed in human SCs. Using antibodies directed against ALDH1 and its isoforms ALDH1A1 and ALDH1A3, respectively, we demonstrate immunohistochemical staining in peri-fascicular position matching the localization of SCs. Consistently, co-immunofluorescence reveals ALDH1 expression in CD56 positive stem cells and co-localization of the isoforms ALDH1A1 and ALDH1A3 in Pax7 positive SCs. Quantitative analysis of immunohistochemical staining showed no significant differences in the distribution of ALDH1 positive SCs in the skeletal muscle groups pectoralis, diaphragm and psoas that have been investigated in the present study. In conclusion, human SCs co-express the ALDH1 isoforms ALDH1A1 and ALDH1A3. Keywords: Satellite Cells • Human Skeletal Muscle • ALDH1 • ALDH1A1 • ALDH1A3 Introduction Here, we show that ALDH1 is expressed in CD56 positive stem cells of human skeletal muscle and that its isoforms ALDH1A1 and ALDH1A3 co-localize with Pax7 positive SCs. -
Transcriptional Silencing of ALDH2 Confers a Dependency on Fanconi Anemia Proteins in Acute Myeloid Leukemia
Author Manuscript Published OnlineFirst on April 23, 2021; DOI: 10.1158/2159-8290.CD-20-1542 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Transcriptional silencing of ALDH2 confers a dependency on Fanconi anemia proteins in acute myeloid leukemia Zhaolin Yang1, Xiaoli S. Wu1,2, Yiliang Wei1, Sofya A. Polyanskaya1, Shruti V. Iyer1,2, Moonjung Jung3, Francis P. Lach3, Emmalee R. Adelman4, Olaf Klingbeil1, Joseph P. Milazzo1, Melissa Kramer1, Osama E. Demerdash1, Kenneth Chang1, Sara Goodwin1, Emily Hodges5, W. Richard McCombie1, Maria E. Figueroa4, Agata Smogorzewska3, and Christopher R. Vakoc1,6* 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA 2Genetics Program, Stony Brook University, Stony Brook, New York 11794, USA 3Laboratory of Genome Maintenance, The Rockefeller University, New York 10065, USA 4Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA 5Department of Biochemistry and Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA 6Lead contact *Correspondence: [email protected]; Christopher R. Vakoc, 1 Bungtown Rd, Cold Spring Harbor, NY 11724. 516-367-5030 Running title: Fanconi anemia pathway dependency in AML Category: Myeloid Neoplasia Keywords: CONFLICT OF INTEREST DISCLOSURES C.R.V. has received consulting fees from Flare Therapeutics, Roivant Sciences, and C4 Therapeutics, has served on the scientific advisory board of KSQ Therapeutics and Syros Pharmaceuticals, and has received research funding from Boehringer-Ingelheim. W.R.M. is a founder and shareholder of Orion Genomics and has received research support from Pacific Biosciences and support for attending meetings from Oxford Nanopore.