NAD Augmentation Ameliorates Acute Pancreatitis Through Regulation of Inflammasome Signalling

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jun 9

PMID 28592850

Citations 16

Authors

Aihua 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

Affiliations

Soon will be listed here.

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.

Citing Articles

Mitochondrial uncoupling protein 2: a central player in pancreatic disease pathophysiology.

Wang K, Zhang L, Deng B, Zhao K, Chen C, Wang W Mol Med. 2024; 30(1):259.

PMID: 39707176 PMC: 11660649. DOI: 10.1186/s10020-024-01027-y.

Chlojaponilactone B Attenuates THP-1 Macrophage Pyroptosis by Inhibiting the TLR/MyD88/NF-κB Pathway.

Wen Q, Zhan B, Jin L, Peng Z, Liu J, Zhu L Pharmaceuticals (Basel). 2024; 17(3).

PMID: 38543188 PMC: 10975068. DOI: 10.3390/ph17030402.

The Role of MicroRNAs in Pancreatitis Development and Progression.

Patel H, Almanzar V, LaComb J, Ju J, Bialkowska A Int J Mol Sci. 2023; 24(2).

PMID: 36674571 PMC: 9862468. DOI: 10.3390/ijms24021057.

Augmentation of NAD by Dunnione Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice.

Lee S, Kim H, Oh G, Lee S, Khadka D, Cao W J Inflamm Res. 2022; 15:4623-4636.

PMID: 35991005 PMC: 9386739. DOI: 10.2147/JIR.S372543.

Beta-Lapachone Attenuates BMSC-Mediated Neuroblastoma Malignant Transformation by Inhibiting Gal-3/Gal-3BP/IL6 Axis.

Zhou Y, Yan H, Zhou Q, Feng R, Wang P, Yang F Front Pharmacol. 2021; 12:766909.

PMID: 34790130 PMC: 8591123. DOI: 10.3389/fphar.2021.766909.

References

Wang Y, Kim N, Haince J, Kang H, David K, Andrabi S . Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal. 2011; 4(167):ra20. PMC: 3086524. DOI: 10.1126/scisignal.2000902. View

Norman J, Fink G, Franz M . Acute pancreatitis induces intrapancreatic tumor necrosis factor gene expression. Arch Surg. 1995; 130(9):966-70. DOI: 10.1001/archsurg.1995.01430090052018. View

Willemer S, Elsasser H, Adler G . Hormone-induced pancreatitis. Eur Surg Res. 1992; 24 Suppl 1:29-39. DOI: 10.1159/000129237. View

Harris H, Andersson U . Mini-review: The nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004; 34(6):1503-12. DOI: 10.1002/eji.200424916. View

Oh G, Kim H, Choi J, Shen A, Choe S, Karna A . Pharmacological activation of NQO1 increases NAD⁺ levels and attenuates cisplatin-mediated acute kidney injury in mice. Kidney Int. 2013; 85(3):547-60. PMC: 3944666. DOI: 10.1038/ki.2013.330. View

Yasuda T, Ueda T, Takeyama Y, Shinzeki M, Sawa H, Nakajima T . Significant increase of serum high-mobility group box chromosomal protein 1 levels in patients with severe acute pancreatitis. Pancreas. 2006; 33(4):359-63. DOI: 10.1097/01.mpa.0000236741.15477.8b. View

Oka S, Hsu C, Sadoshima J . Regulation of cell survival and death by pyridine nucleotides. Circ Res. 2012; 111(5):611-27. PMC: 3523888. DOI: 10.1161/CIRCRESAHA.111.247932. View

Sawa H, Ueda T, Takeyama Y, Yasuda T, Shinzeki M, Nakajima T . Role of toll-like receptor 4 in the pathophysiology of severe acute pancreatitis in mice. Surg Today. 2007; 37(10):867-73. DOI: 10.1007/s00595-007-3520-x. View

Li Y, Zhou Z, Xia Q, Zhang J, Li H, Cao G . Toll-like receptor 4 detected in exocrine pancreas and the change of expression in cerulein-induced pancreatitis. Pancreas. 2005; 30(4):375-81. DOI: 10.1097/01.mpa.0000160959.21580.41. View

10.

Cui X, Chen Q, Dong Z, Xu L, Lu T, Li D . Inactivation of Sirt1 in mouse livers protects against endotoxemic liver injury by acetylating and activating NF-κB. Cell Death Dis. 2016; 7(10):e2403. PMC: 5133964. DOI: 10.1038/cddis.2016.270. View

11.

Byun S, Son Y, Cho B, Chung H, Pae H . β-Lapachone, a substrate of NAD(P)H:quinone oxidoreductase, induces anti-inflammatory heme oxygenase-1 via AMP-activated protein kinase activation in RAW264.7 macrophages. J Clin Biochem Nutr. 2013; 52(2):106-11. PMC: 3593126. DOI: 10.3164/jcbn.12-80. View

12.

Gravante G, Garcea G, Ong S, Metcalfe M, Berry D, Lloyd D . Prediction of mortality in acute pancreatitis: a systematic review of the published evidence. Pancreatology. 2009; 9(5):601-14. DOI: 10.1159/000212097. View

13.

Kim H, Oh G, Shen A, Lee S, Choe S, Kwon K . Augmentation of NAD(+) by NQO1 attenuates cisplatin-mediated hearing impairment. Cell Death Dis. 2014; 5:e1292. PMC: 4611728. DOI: 10.1038/cddis.2014.255. View

14.

Gross O, Thomas C, Guarda G, Tschopp J . The inflammasome: an integrated view. Immunol Rev. 2011; 243(1):136-51. DOI: 10.1111/j.1600-065X.2011.01046.x. View

15.

Medzhitov R, Janeway Jr C . Decoding the patterns of self and nonself by the innate immune system. Science. 2002; 296(5566):298-300. DOI: 10.1126/science.1068883. View

16.

Kubes P, Mehal W . Sterile inflammation in the liver. Gastroenterology. 2012; 143(5):1158-1172. DOI: 10.1053/j.gastro.2012.09.008. View

17.

Rabadi M, Xavier S, Vasko R, Kaur K, Goligorksy M, Ratliff B . High-mobility group box 1 is a novel deacetylation target of Sirtuin1. Kidney Int. 2014; 87(1):95-108. PMC: 4270955. DOI: 10.1038/ki.2014.217. View

18.

Gardella S, Andrei C, Ferrera D, Lotti L, Torrisi M, Bianchi M . The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 2002; 3(10):995-1001. PMC: 1307617. DOI: 10.1093/embo-reports/kvf198. View

19.

Xu W, Lu Y, Yao J, Li Z, Chen Z, Wang G . Novel role of resveratrol: suppression of high-mobility group protein box 1 nucleocytoplasmic translocation by the upregulation of sirtuin 1 in sepsis-induced liver injury. Shock. 2014; 42(5):440-7. DOI: 10.1097/SHK.0000000000000225. View

20.

Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A . TLR9 and the NLRP3 inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology. 2011; 141(1):358-69. PMC: 3129497. DOI: 10.1053/j.gastro.2011.03.041. View