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An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease

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 aci...

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Autores principales: Cuomo, Paola, Papaianni, Marina, Sansone, Clementina, Iannelli, Antonio, Iannelli, Domenico, Medaglia, Chiara, Paris, Debora, Motta, Andrea, Capparelli, Rosanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664682/
https://www.ncbi.nlm.nih.gov/pubmed/33171588
http://dx.doi.org/10.3390/ijms21218369
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author Cuomo, Paola
Papaianni, Marina
Sansone, Clementina
Iannelli, Antonio
Iannelli, Domenico
Medaglia, Chiara
Paris, Debora
Motta, Andrea
Capparelli, Rosanna
author_facet Cuomo, Paola
Papaianni, Marina
Sansone, Clementina
Iannelli, Antonio
Iannelli, Domenico
Medaglia, Chiara
Paris, Debora
Motta, Andrea
Capparelli, Rosanna
author_sort Cuomo, Paola
collection PubMed
description 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.
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spelling pubmed-76646822020-11-14 An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease Cuomo, Paola Papaianni, Marina Sansone, Clementina Iannelli, Antonio Iannelli, Domenico Medaglia, Chiara Paris, Debora Motta, Andrea Capparelli, Rosanna Int J Mol Sci Article 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. MDPI 2020-11-08 /pmc/articles/PMC7664682/ /pubmed/33171588 http://dx.doi.org/10.3390/ijms21218369 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cuomo, Paola
Papaianni, Marina
Sansone, Clementina
Iannelli, Antonio
Iannelli, Domenico
Medaglia, Chiara
Paris, Debora
Motta, Andrea
Capparelli, Rosanna
An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title_full An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title_fullStr An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title_full_unstemmed An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title_short An In Vitro Model to Investigate the Role of Helicobacter Pylori in Type 2 Diabetes, Obesity, Alzheimer’s Disease and Cardiometabolic Disease
title_sort in vitro model to investigate the role of helicobacter pylori in type 2 diabetes, obesity, alzheimer’s disease and cardiometabolic disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664682/
https://www.ncbi.nlm.nih.gov/pubmed/33171588
http://dx.doi.org/10.3390/ijms21218369
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