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NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling

Title
NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
Authors
Shen A.Kim H.-J.Oh G.-S.Lee S.-B.Lee S.H.Pandit A.Khadka D.Choe S.-K.Kwak S.C.Yang S.-H.Cho E.-Y.Kim H.-S.Kim H.Park R.Kwak T.H.So H.-S.
Ewha Authors
김현석
SCOPUS Author ID
김현석scopus
Issue Date
2017
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 7, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © The Author(s) 2017.
DOI
10.1038/s41598-017-03418-0
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일반대학원 > 바이오융합과학과 > Journal papers
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