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Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice
Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-kn...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315021/ https://www.ncbi.nlm.nih.gov/pubmed/30584237 http://dx.doi.org/10.1038/s41419-018-1252-z |
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author | Shen, AiHua Kim, Hyung-Jin Oh, Gi-Su Lee, Su-Bin Lee, SeungHoon Pandit, Arpana Khadka, Dipendra Sharma, Subham Kim, Seon Young Choe, Seong-Kyu Yang, Sei-Hoon Cho, Eun-Young Shim, Hyuk Park, Raekil Kwak, Tae Hwan So, Hong-Seob |
author_facet | Shen, AiHua Kim, Hyung-Jin Oh, Gi-Su Lee, Su-Bin Lee, SeungHoon Pandit, Arpana Khadka, Dipendra Sharma, Subham Kim, Seon Young Choe, Seong-Kyu Yang, Sei-Hoon Cho, Eun-Young Shim, Hyuk Park, Raekil Kwak, Tae Hwan So, Hong-Seob |
author_sort | Shen, AiHua |
collection | PubMed |
description | Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), reduces the ratio of cellular NADPH/NADP(+) through the enzymatic action of NQO1. This study assessed whether a reduction in cellular NADPH/NADP(+) ratio can be used to regulate caerulein-induced pancreatic damage associated with NOX-induced ROS production in animal models. Dunnione treatment significantly reduced the cellular NADPH/NADP(+) ratio and NOX activity through the enzymatic action of NQO1 in the pancreas of the caerulein-injection group. Similar to these results, total ROS production and expressions of mRNA and protein for NOX subunits Nox1, p27(phox), p47(phox), and p67(phox) also decreased in the dunnione-treated group. In addition, caerulein-induced pancreatic inflammation and acinar cell injury were significantly reduced by dunnione treatment. This study is the first to demonstrate that modulation of the cellular NADPH:NADP(+) ratio by enzymatic action of NQO1 protects acute pancreatitis through the regulation of NOX activity. Furthermore, these results suggest that modulation of the NADPH:NADP(+) ratio in cells by NQO1 may be a novel therapeutic strategy for acute pancreatitis. |
format | Online Article Text |
id | pubmed-6315021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63150212019-01-03 Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice Shen, AiHua Kim, Hyung-Jin Oh, Gi-Su Lee, Su-Bin Lee, SeungHoon Pandit, Arpana Khadka, Dipendra Sharma, Subham Kim, Seon Young Choe, Seong-Kyu Yang, Sei-Hoon Cho, Eun-Young Shim, Hyuk Park, Raekil Kwak, Tae Hwan So, Hong-Seob Cell Death Dis Article Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), reduces the ratio of cellular NADPH/NADP(+) through the enzymatic action of NQO1. This study assessed whether a reduction in cellular NADPH/NADP(+) ratio can be used to regulate caerulein-induced pancreatic damage associated with NOX-induced ROS production in animal models. Dunnione treatment significantly reduced the cellular NADPH/NADP(+) ratio and NOX activity through the enzymatic action of NQO1 in the pancreas of the caerulein-injection group. Similar to these results, total ROS production and expressions of mRNA and protein for NOX subunits Nox1, p27(phox), p47(phox), and p67(phox) also decreased in the dunnione-treated group. In addition, caerulein-induced pancreatic inflammation and acinar cell injury were significantly reduced by dunnione treatment. This study is the first to demonstrate that modulation of the cellular NADPH:NADP(+) ratio by enzymatic action of NQO1 protects acute pancreatitis through the regulation of NOX activity. Furthermore, these results suggest that modulation of the NADPH:NADP(+) ratio in cells by NQO1 may be a novel therapeutic strategy for acute pancreatitis. Nature Publishing Group UK 2018-12-18 /pmc/articles/PMC6315021/ /pubmed/30584237 http://dx.doi.org/10.1038/s41419-018-1252-z Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Shen, AiHua Kim, Hyung-Jin Oh, Gi-Su Lee, Su-Bin Lee, SeungHoon Pandit, Arpana Khadka, Dipendra Sharma, Subham Kim, Seon Young Choe, Seong-Kyu Yang, Sei-Hoon Cho, Eun-Young Shim, Hyuk Park, Raekil Kwak, Tae Hwan So, Hong-Seob Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title | Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title_full | Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title_fullStr | Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title_full_unstemmed | Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title_short | Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice |
title_sort | pharmacological stimulation of nqo1 decreases nadph levels and ameliorates acute pancreatitis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315021/ https://www.ncbi.nlm.nih.gov/pubmed/30584237 http://dx.doi.org/10.1038/s41419-018-1252-z |
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