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

作者：Shen AiHua; Kim Hyung Jin; Oh Gi Su; Lee Su Bin; Lee Seung Hoon; Pandit Arpana; Khadka Dipendra; Choe Seong Kyu; Kwak Sung Chul; Yang Sei Hoon; Cho Eun Young; Kim Hyun Seok; Kim Hail; Park Raekil; Kwak Tae Hwan; So Hong Seob

来源：Scientific Reports, 2017, 7(1): 3006.

DOI：10.1038/s41598-017-03418-0

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.

• 出版日期2017-6-7