NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling

Ai Hua 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

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24 Scopus citations

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.

Original languageEnglish
Article number3006
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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