NAD+ augmentation ameliorates acute pancreatitis through regulation of inflammasome signalling
| Autor: | Seung-Hoon Lee, Seong Kyu Choe, Sung Chul Kwak, Hail Kim, Arpana Pandit, Dipendra Khadka, Sei Hoon Yang, Hyungjin Kim, Tae Hwan Kwak, S.-B. Lee, Hyun-Seok Kim, Raekil Park, Ai Hua Shen, Eun Young Cho, Gi Su Oh, Hong Seob So |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Programmed cell death Multidisciplinary biology Science Inflammasome Nicotinamide adenine dinucleotide Cofactor Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Biochemistry chemistry medicine biology.protein Medicine NAD+ kinase Signal transduction Intracellular Homeostasis medicine.drug |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) SCIENTIFIC REPORTS(7) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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