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Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells

Continuous free radical assault upsets cellular homeostasis and dysregulates associated signaling pathways to promote stress-induced cell death. In spite of the continuous development and implementation of effective therapeutic strategies, limitations in treatments for stress-induced toxicities rema...

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Autores principales: Roy Chowdhury, Sougata, Sengupta, Suman, Biswas, Subir, Sinha, Tridib Kumar, Sen, Ramkrishna, Basak, Ratan Kumar, Adhikari, Basudam, Bhattacharyya, Arindam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239092/
https://www.ncbi.nlm.nih.gov/pubmed/25412177
http://dx.doi.org/10.1371/journal.pone.0113663
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author Roy Chowdhury, Sougata
Sengupta, Suman
Biswas, Subir
Sinha, Tridib Kumar
Sen, Ramkrishna
Basak, Ratan Kumar
Adhikari, Basudam
Bhattacharyya, Arindam
author_facet Roy Chowdhury, Sougata
Sengupta, Suman
Biswas, Subir
Sinha, Tridib Kumar
Sen, Ramkrishna
Basak, Ratan Kumar
Adhikari, Basudam
Bhattacharyya, Arindam
author_sort Roy Chowdhury, Sougata
collection PubMed
description Continuous free radical assault upsets cellular homeostasis and dysregulates associated signaling pathways to promote stress-induced cell death. In spite of the continuous development and implementation of effective therapeutic strategies, limitations in treatments for stress-induced toxicities remain. The purpose of the present study was to determine the potential therapeutic efficacy of bacterial fucose polysaccharides against hydrogen peroxide (H(2)O(2))-induced stress in human lung fibroblast (WI38) cells and to understand the associated molecular mechanisms. In two different fermentation processes, Bacillus megaterium RB-05 biosynthesized two non-identical fucose polysaccharides; of these, the polysaccharide having a high-fucose content (∼42%) conferred the maximum free radical scavenging efficiency in vitro. Structural characterizations of the purified polysaccharides were performed using HPLC, GC-MS, and (1)H/(13)C/2D-COSY NMR. H(2)O(2) (300 µM) insult to WI38 cells showed anti-proliferative effects by inducing intracellular reactive oxygen species (ROS) and by disrupting mitochondrial membrane permeability, followed by apoptosis. The polysaccharide (250 µg/mL) attenuated the cell death process by directly scavenging intracellular ROS rather than activating endogenous antioxidant enzymes. This process encompasses inhibition of caspase-9/3/7, a decrease in the ratio of Bax/Bcl2, relocalization of translocated Bax and cytochrome c, upregulation of anti-apoptotic members of the Bcl2 family and a decrease in the phosphorylation of MAPKs (mitogen activated protein kinases). Furthermore, cellular homeostasis was re-established via stabilization of MAPK-mediated Nrf2/Keap1 signaling and transcription of downstream cytoprotective genes. This molecular study uniquely introduces a fucose-rich bacterial polysaccharide as a potential inhibitor of H(2)O(2)-induced stress and toxicities.
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spelling pubmed-42390922014-11-26 Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells Roy Chowdhury, Sougata Sengupta, Suman Biswas, Subir Sinha, Tridib Kumar Sen, Ramkrishna Basak, Ratan Kumar Adhikari, Basudam Bhattacharyya, Arindam PLoS One Research Article Continuous free radical assault upsets cellular homeostasis and dysregulates associated signaling pathways to promote stress-induced cell death. In spite of the continuous development and implementation of effective therapeutic strategies, limitations in treatments for stress-induced toxicities remain. The purpose of the present study was to determine the potential therapeutic efficacy of bacterial fucose polysaccharides against hydrogen peroxide (H(2)O(2))-induced stress in human lung fibroblast (WI38) cells and to understand the associated molecular mechanisms. In two different fermentation processes, Bacillus megaterium RB-05 biosynthesized two non-identical fucose polysaccharides; of these, the polysaccharide having a high-fucose content (∼42%) conferred the maximum free radical scavenging efficiency in vitro. Structural characterizations of the purified polysaccharides were performed using HPLC, GC-MS, and (1)H/(13)C/2D-COSY NMR. H(2)O(2) (300 µM) insult to WI38 cells showed anti-proliferative effects by inducing intracellular reactive oxygen species (ROS) and by disrupting mitochondrial membrane permeability, followed by apoptosis. The polysaccharide (250 µg/mL) attenuated the cell death process by directly scavenging intracellular ROS rather than activating endogenous antioxidant enzymes. This process encompasses inhibition of caspase-9/3/7, a decrease in the ratio of Bax/Bcl2, relocalization of translocated Bax and cytochrome c, upregulation of anti-apoptotic members of the Bcl2 family and a decrease in the phosphorylation of MAPKs (mitogen activated protein kinases). Furthermore, cellular homeostasis was re-established via stabilization of MAPK-mediated Nrf2/Keap1 signaling and transcription of downstream cytoprotective genes. This molecular study uniquely introduces a fucose-rich bacterial polysaccharide as a potential inhibitor of H(2)O(2)-induced stress and toxicities. Public Library of Science 2014-11-20 /pmc/articles/PMC4239092/ /pubmed/25412177 http://dx.doi.org/10.1371/journal.pone.0113663 Text en © 2014 Roy Chowdhury et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Roy Chowdhury, Sougata
Sengupta, Suman
Biswas, Subir
Sinha, Tridib Kumar
Sen, Ramkrishna
Basak, Ratan Kumar
Adhikari, Basudam
Bhattacharyya, Arindam
Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title_full Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title_fullStr Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title_full_unstemmed Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title_short Bacterial Fucose-Rich Polysaccharide Stabilizes MAPK-Mediated Nrf2/Keap1 Signaling by Directly Scavenging Reactive Oxygen Species during Hydrogen Peroxide-Induced Apoptosis of Human Lung Fibroblast Cells
title_sort bacterial fucose-rich polysaccharide stabilizes mapk-mediated nrf2/keap1 signaling by directly scavenging reactive oxygen species during hydrogen peroxide-induced apoptosis of human lung fibroblast cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239092/
https://www.ncbi.nlm.nih.gov/pubmed/25412177
http://dx.doi.org/10.1371/journal.pone.0113663
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