Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.

Humans Animals Mice Spermidine / pharmacology Proteomics Peptide Initiation Factors / genetics Carcinogenesis / genetics Colitis / chemically induced Homeostasis Inflammation
Colon Cancer Hypusine Inflammation Intestinal Epithelial Cells

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
09 2023
Historique:
received: 29 09 2022
revised: 19 04 2023
accepted: 25 05 2023
pmc-release: 01 09 2024
medline: 22 8 2023
pubmed: 5 6 2023
entrez: 4 6 2023
Statut: ppublish

Résumé

The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5A We used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis. We found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5A Hypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.

Sections du résumé

BACKGROUND & AIMS
The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5A
METHODS
We used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis.
RESULTS
We found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5A
CONCLUSIONS
Hypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.

Identifiants

DOI: 10.1053/j.gastro.2023.05.041 PMID: 37271289 PMC: PMC10527201
pubmed: 37271289
pii: S0016-5085(23)00814-4
doi: 10.1053/j.gastro.2023.05.041
pmc: PMC10527201
mid: NIHMS1907400
pii:
doi:

Substances chimiques

Spermidine U87FK77H25
Peptide Initiation Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

656-669.e8

Subventions

Organisme : NCI NIH HHS
ID : P01 CA028842
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128200
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK123495
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK058404
Pays : United States
Organisme : NCI NIH HHS
ID : R41 CA257262
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA116087
Pays : United States
Organisme : BLRD VA
ID : I01 BX004366
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124906
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020595
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK060581
Pays : United States
Organisme : CSRD VA
ID : I01 CX002473
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI138932
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA183727
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA068485
Pays : United States
Organisme : CSRD VA
ID : I01 CX002171
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009592
Pays : United States

Informations de copyright

Published by Elsevier Inc.

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Auteurs

Alain P Gobert (AP)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: alain.p.gobert@vumc.org.

Thaddeus M Smith (TM)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Yvonne L Latour (YL)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Mohammad Asim (M)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Daniel P Barry (DP)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Margaret M Allaman (MM)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Kamery J Williams (KJ)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Kara M McNamara (KM)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.

Alberto G Delgado (AG)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Sarah P Short (SP)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.

Raghavendra G Mirmira (RG)

Kovler Diabetes Center, Department of Medicine, The University of Chicago, Chicago, Illinois.

Kristie L Rose (KL)

Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Kevin L Schey (KL)

Department of Biochemistry, Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Irene Zagol-Ikapitte (I)

Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Jeremy S Coleman (JS)

Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Olivier Boutaud (O)

Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Shilin Zhao (S)

Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.

M Blanca Piazuelo (MB)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee.

M Kay Washington (MK)

Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Lori A Coburn (LA)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee.

Keith T Wilson (KT)

Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee. Electronic address: keith.wilson@vumc.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Eucaryotes › Animaux › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Composés chimiques organiques › Amines › Polyamines › Spermidine › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines ribosomiques › Facteurs initiation chaîne peptidique › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du côlon › Colite › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › Phénomènes physiologiques › Homéostasie › Hypusination Maintains Intestinal Homeostasis...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Hypusination Maintains Intestinal Homeostasis...