An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer's Disease and Cardiometabolic Disease.
Identifieur interne : 000152 ( Main/Exploration ); précédent : 000151; suivant : 000153An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer's Disease and Cardiometabolic Disease.
Auteurs : Paola Cuomo [Italie] ; Marina Papaianni [Italie] ; Clementina Sansone [Italie] ; Antonio Iannelli [France] ; Domenico Iannelli [Italie] ; Chiara Medaglia [Suisse] ; Debora Paris [Italie] ; Andrea Motta [Italie] ; Rosanna Capparelli [Italie]Source :
- International journal of molecular sciences [ 1422-0067 ] ; 2020.
Abstract
Helicobacter pylori (Hp) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the Hp cell filtrate (Hpcf) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer's diseases, and cardiometabolic disease. Here, we demonstrate how Hp may modulate these traits. Hp induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by Hp. Furthermore, Hp modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the Hp toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how Hp may potentially manipulate them.
DOI: 10.3390/ijms21218369
PubMed: 33171588
PubMed Central: PMC7664682
Affiliations:
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first="Paola" last="Cuomo">Paola Cuomo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples</wicri:regionArea><wicri:noRegion>80055 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Papaianni, Marina" sort="Papaianni, Marina" uniqKey="Papaianni M" first="Marina" last="Papaianni">Marina Papaianni</name><affiliation wicri:level="1"><nlm:affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples</wicri:regionArea><wicri:noRegion>80055 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Sansone, Clementina" sort="Sansone, Clementina" uniqKey="Sansone C" first="Clementina" last="Sansone">Clementina Sansone</name><affiliation wicri:level="1"><nlm:affiliation>Department of Marine Biotechnology, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Marine Biotechnology, Stazione Zoologica Anton Dohrn, 80121 Naples</wicri:regionArea><wicri:noRegion>80121 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Iannelli, Antonio" sort="Iannelli, Antonio" uniqKey="Iannelli A" first="Antonio" last="Iannelli">Antonio Iannelli</name><affiliation wicri:level="3"><nlm:affiliation>Department of Digestive Surgery, Université Côte d'Azur, Campus Valrose, Batiment L, Avenue de Valrose, 28-CEDEX 2, 06108 Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Digestive Surgery, Université Côte d'Azur, Campus Valrose, Batiment L, Avenue de Valrose, 28-CEDEX 2, 06108 Nice</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Inserm, U1065, Team 8 "Hepatic Complications of Obesity and Alcohol", Route Saint Antoine de Ginestière 151, BP 2 3194, CEDEX 3, 06204 Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U1065, Team 8 "Hepatic Complications of Obesity and Alcohol", Route Saint Antoine de Ginestière 151, BP 2 3194, CEDEX 3, 06204 Nice</wicri:regionArea><placeName><region type="region" nuts="2">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Iannelli, Domenico" sort="Iannelli, Domenico" uniqKey="Iannelli D" first="Domenico" last="Iannelli">Domenico Iannelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples</wicri:regionArea><wicri:noRegion>80055 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Medaglia, Chiara" sort="Medaglia, Chiara" uniqKey="Medaglia C" first="Chiara" last="Medaglia">Chiara Medaglia</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Molecular Medicine, University of Geneva Medical School, rue du Général-Dufour, 1211 Genève, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Department of Microbiology and Molecular Medicine, University of Geneva Medical School, rue du Général-Dufour, 1211 Genève</wicri:regionArea><wicri:noRegion>1211 Genève</wicri:noRegion></affiliation></author><author><name sortKey="Paris, Debora" sort="Paris, Debora" uniqKey="Paris D" first="Debora" last="Paris">Debora Paris</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples</wicri:regionArea><wicri:noRegion>80078 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Motta, Andrea" sort="Motta, Andrea" uniqKey="Motta A" first="Andrea" last="Motta">Andrea Motta</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples</wicri:regionArea><wicri:noRegion>80078 Naples</wicri:noRegion></affiliation></author><author><name sortKey="Capparelli, Rosanna" sort="Capparelli, Rosanna" uniqKey="Capparelli R" first="Rosanna" last="Capparelli">Rosanna Capparelli</name><affiliation wicri:level="1"><nlm:affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples</wicri:regionArea><wicri:noRegion>80055 Naples</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of molecular sciences</title><idno type="eISSN">1422-0067</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><i>Helicobacter pylori</i> (<i>Hp</i>) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the <i>Hp</i> cell filtrate (<i>Hpcf</i>) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer's diseases, and cardiometabolic disease. Here, we demonstrate how <i>Hp</i> may modulate these traits. <i>Hp</i> induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by <i>Hp</i>. Furthermore, <i>Hp</i> modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the <i>Hp</i> toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how <i>Hp</i> may potentially manipulate them.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">33171588</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>14</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1422-0067</ISSN><JournalIssue CitedMedium="Internet"><Volume>21</Volume><Issue>21</Issue><PubDate><Year>2020</Year><Month>Nov</Month><Day>08</Day></PubDate></JournalIssue><Title>International journal of molecular sciences</Title><ISOAbbreviation>Int J Mol Sci</ISOAbbreviation></Journal><ArticleTitle>An In Vitro Model to Investigate the Role of <i>Helicobacter Pylori</i> in Type 2 Diabetes, Obesity, Alzheimer's Disease and Cardiometabolic Disease.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E8369</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/ijms21218369</ELocationID><Abstract><AbstractText><i>Helicobacter pylori</i> (<i>Hp</i>) is a Gram-negative bacterium colonizing the human stomach. Nuclear Magnetic Resonance (NMR) analysis of intracellular human gastric carcinoma cells (MKN-28) incubated with the <i>Hp</i> cell filtrate (<i>Hpcf</i>) displays high levels of amino acids, including the branched chain amino acids (BCAA) isoleucine, leucine, and valine. Polymerase chain reaction (PCR) Array Technology shows upregulation of mammalian Target Of Rapamycin Complex 1 (mTORC1), inflammation, and mitochondrial dysfunction. The review of literature indicates that these traits are common to type 2 diabetes, obesity, Alzheimer's diseases, and cardiometabolic disease. Here, we demonstrate how <i>Hp</i> may modulate these traits. <i>Hp</i> induces high levels of amino acids, which, in turn, activate mTORC1, which is the complex regulating the metabolism of the host. A high level of BCAA and upregulation of mTORC1 are, thus, directly regulated by <i>Hp</i>. Furthermore, <i>Hp</i> modulates inflammation, which is functional to the persistence of chronic infection and the asymptomatic state of the host. Finally, in order to induce autophagy and sustain bacterial colonization of gastric mucosa, the <i>Hp</i> toxin VacA localizes within mitochondria, causing fragmentation of these organelles, depletion of ATP, and oxidative stress. In conclusion, our in vitro disease model replicates the main traits common to the above four diseases and shows how <i>Hp</i> may potentially manipulate them.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cuomo</LastName><ForeName>Paola</ForeName><Initials>P</Initials><Identifier Source="ORCID">0000-0003-4504-1714</Identifier><AffiliationInfo><Affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Papaianni</LastName><ForeName>Marina</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sansone</LastName><ForeName>Clementina</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Marine Biotechnology, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iannelli</LastName><ForeName>Antonio</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Digestive Surgery, Université Côte d'Azur, Campus Valrose, Batiment L, Avenue de Valrose, 28-CEDEX 2, 06108 Nice, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Inserm, U1065, Team 8 "Hepatic Complications of Obesity and Alcohol", Route Saint Antoine de Ginestière 151, BP 2 3194, CEDEX 3, 06204 Nice, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Iannelli</LastName><ForeName>Domenico</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Medaglia</LastName><ForeName>Chiara</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Molecular Medicine, University of Geneva Medical School, rue du Général-Dufour, 1211 Genève, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paris</LastName><ForeName>Debora</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Motta</LastName><ForeName>Andrea</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-8643-658X</Identifier><AffiliationInfo><Affiliation>Institute of Biomolecular Chemistry, National Research Council, via Campi Flegrei, 34-Pozzuoli, 80078 Naples, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Capparelli</LastName><ForeName>Rosanna</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Agriculture Sciences, University of Naples "Federico II", via Università, 100-Portici, 80055 Naples, Italy.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>11</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Int J Mol Sci</MedlineTA><NlmUniqueID>101092791</NlmUniqueID><ISSNLinking>1422-0067</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Helicobacter pylori</Keyword><Keyword MajorTopicYN="N">branched chain amino acids</Keyword><Keyword MajorTopicYN="N">inflammation</Keyword><Keyword MajorTopicYN="N">mTORC1</Keyword><Keyword 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Antonio" uniqKey="Iannelli A" first="Antonio" last="Iannelli">Antonio Iannelli</name></region><name sortKey="Iannelli, Antonio" sort="Iannelli, Antonio" uniqKey="Iannelli A" first="Antonio" last="Iannelli">Antonio Iannelli</name></country><country name="Suisse"><noRegion><name sortKey="Medaglia, Chiara" sort="Medaglia, Chiara" uniqKey="Medaglia C" first="Chiara" last="Medaglia">Chiara Medaglia</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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