Pharmacological stimulation of NQO1 decreases NADPH levels and ameliorates acute pancreatitis in mice
| Autor: | Dipendra Khadka, SeungHoon Lee, AiHua Shen, Sei-Hoon Yang, Arpana Pandit, Eun Young Cho, Seong-Kyu Choe, Gi-Su Oh, Seon Young Kim, Hyung-Jin Kim, Raekil Park, Hyuk Shim, Hong-Seob So, Su-Bin Lee, Subham Sharma, Tae Hwan Kwak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cancer Research Immunology Pharmacology Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Downregulation and upregulation NAD(P)H Dehydrogenase (Quinone) medicine Acinar cell Animals lcsh:QH573-671 Mice Knockout chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology lcsh:Cytology Cell Biology medicine.disease 030104 developmental biology Enzyme Pancreatitis chemistry NOX1 biology.protein 030211 gastroenterology & hepatology NAD+ kinase Reactive Oxygen Species Ceruletide NADP Naphthoquinones |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 1, Pp 1-11 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Reactive oxygen species (ROS) regulates the activation of inflammatory cascades and tissue damage in acute pancreatitis. NADPH oxidase (NOX) is upregulated in pancreatitis and is one of the major enzymes involved in ROS production using NADPH as a general rate-limiting substrate. Dunnione, a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), reduces the ratio of cellular NADPH/NADP+ through the enzymatic action of NQO1. This study assessed whether a reduction in cellular NADPH/NADP+ ratio can be used to regulate caerulein-induced pancreatic damage associated with NOX-induced ROS production in animal models. Dunnione treatment significantly reduced the cellular NADPH/NADP+ ratio and NOX activity through the enzymatic action of NQO1 in the pancreas of the caerulein-injection group. Similar to these results, total ROS production and expressions of mRNA and protein for NOX subunits Nox1, p27phox, p47phox, and p67phox also decreased in the dunnione-treated group. In addition, caerulein-induced pancreatic inflammation and acinar cell injury were significantly reduced by dunnione treatment. This study is the first to demonstrate that modulation of the cellular NADPH:NADP+ ratio by enzymatic action of NQO1 protects acute pancreatitis through the regulation of NOX activity. Furthermore, these results suggest that modulation of the NADPH:NADP+ ratio in cells by NQO1 may be a novel therapeutic strategy for acute pancreatitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|