NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling

Abstract Acute pancreatitis (AP) is a complicated disease without specific drug therapy. The cofactor nicotinamide adenine dinucleotide (NAD+) is an important regulator of cellular metabolism and homeostasis. However, it remains unclear whether modulation of NAD+ levels has an impact on caerulein-in...

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Autores principales:	AiHua Shen, Hyung-Jin Kim, Gi-Su Oh, Su-Bin Lee, Seung Hoon Lee, Arpana Pandit, Dipendra Khadka, Seong-Kyu Choe, Sung Chul Kwak, Sei-Hoon Yang, Eun-Young Cho, Hyun-Seok Kim, Hail Kim, Raekil Park, Tae Hwan Kwak, Hong-Seob So
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a7012ccbdf9e48b2bfc3a7ac7980c0c4
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spelling	oai:doaj.org-article:a7012ccbdf9e48b2bfc3a7ac7980c0c42021-12-02T15:05:54ZNAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling10.1038/s41598-017-03418-02045-2322https://doaj.org/article/a7012ccbdf9e48b2bfc3a7ac7980c0c42017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03418-0https://doaj.org/toc/2045-2322Abstract Acute pancreatitis (AP) is a complicated disease without specific drug therapy. The cofactor nicotinamide adenine dinucleotide (NAD+) is an important regulator of cellular metabolism and homeostasis. However, it remains unclear whether modulation of NAD+ levels has an impact on caerulein-induced AP. Therefore, in this study, we investigated the effect of increased cellular NAD+ levels on caerulein-induced AP. We demonstrated for the first time that the activities and expression of SIRT1 were suppressed by reduction of intracellular NAD+ levels and the p53-microRNA-34a pathway in caerulein-induced AP. Moreover, we confirmed that the increase of cellular NAD+ by NQO1 enzymatic action using the substrate β-Lapachone suppressed caerulein-induced AP with down-regulating TLR4-mediated inflammasome signalling, and thereby reducing the inflammatory responses and pancreatic cell death. These results suggest that pharmacological stimulation of NQO1 could be a promising therapeutic strategy to protect against pathological tissue damage in AP.AiHua ShenHyung-Jin KimGi-Su OhSu-Bin LeeSeung Hoon LeeArpana PanditDipendra KhadkaSeong-Kyu ChoeSung Chul KwakSei-Hoon YangEun-Young ChoHyun-Seok KimHail KimRaekil ParkTae Hwan KwakHong-Seob SoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q AiHua Shen Hyung-Jin Kim Gi-Su Oh Su-Bin Lee Seung Hoon Lee Arpana Pandit Dipendra Khadka Seong-Kyu Choe Sung Chul Kwak Sei-Hoon Yang Eun-Young Cho Hyun-Seok Kim Hail Kim Raekil Park Tae Hwan Kwak Hong-Seob So NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
description	Abstract Acute pancreatitis (AP) is a complicated disease without specific drug therapy. The cofactor nicotinamide adenine dinucleotide (NAD+) is an important regulator of cellular metabolism and homeostasis. However, it remains unclear whether modulation of NAD+ levels has an impact on caerulein-induced AP. Therefore, in this study, we investigated the effect of increased cellular NAD+ levels on caerulein-induced AP. We demonstrated for the first time that the activities and expression of SIRT1 were suppressed by reduction of intracellular NAD+ levels and the p53-microRNA-34a pathway in caerulein-induced AP. Moreover, we confirmed that the increase of cellular NAD+ by NQO1 enzymatic action using the substrate β-Lapachone suppressed caerulein-induced AP with down-regulating TLR4-mediated inflammasome signalling, and thereby reducing the inflammatory responses and pancreatic cell death. These results suggest that pharmacological stimulation of NQO1 could be a promising therapeutic strategy to protect against pathological tissue damage in AP.
format	article
author	AiHua Shen Hyung-Jin Kim Gi-Su Oh Su-Bin Lee Seung Hoon Lee Arpana Pandit Dipendra Khadka Seong-Kyu Choe Sung Chul Kwak Sei-Hoon Yang Eun-Young Cho Hyun-Seok Kim Hail Kim Raekil Park Tae Hwan Kwak Hong-Seob So
author_facet	AiHua Shen Hyung-Jin Kim Gi-Su Oh Su-Bin Lee Seung Hoon Lee Arpana Pandit Dipendra Khadka Seong-Kyu Choe Sung Chul Kwak Sei-Hoon Yang Eun-Young Cho Hyun-Seok Kim Hail Kim Raekil Park Tae Hwan Kwak Hong-Seob So
author_sort	AiHua Shen
title	NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
title_short	NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
title_full	NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
title_fullStr	NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
title_full_unstemmed	NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
title_sort	nad+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a7012ccbdf9e48b2bfc3a7ac7980c0c4
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NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling

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