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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
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.
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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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