NAD(+) augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling

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 beta-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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2017-06
Language
English
Keywords

NUCLEAR-PROTEIN HMGB1; NF-KAPPA-B; NLRP3 INFLAMMASOME; BETA-LAPACHONE; NAD(P)HQUINONE OXIDOREDUCTASE; PYRIDINE-NUCLEOTIDES; LIVER-INJURY; CELL-DEATH; SIRTUIN 1; ACTIVATION

Citation

SCIENTIFIC REPORTS, v.7

ISSN
2045-2322
DOI
10.1038/s41598-017-03418-0
URI
http://hdl.handle.net/10203/224727
Appears in Collection
MSE-Journal Papers(저널논문)
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