Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783609883507032064 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7664682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cuomopaola aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT papaiannimarina aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT sansoneclementina aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT iannelliantonio aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT iannellidomenico aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT medagliachiara aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT parisdebora aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT mottaandrea aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT capparellirosanna aninvitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT cuomopaola invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT papaiannimarina invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT sansoneclementina invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT iannelliantonio invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT iannellidomenico invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT medagliachiara invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT parisdebora invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT mottaandrea invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease AT capparellirosanna invitromodeltoinvestigatetheroleofhelicobacterpyloriintype2diabetesobesityalzheimersdiseaseandcardiometabolicdisease |