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- Title
TMAO promotes apoptosis and oxidative stress of pancreatic acinar cells by mediating IRE1α-XBP-1 pathway.
- Authors
Yang, Guodong; Zhang, Xiaoying
- Abstract
Background: Acute pancreatitis caused by hyperlipidemia is a severe life-threatening condition. Therefore, it is urgent to develop new therapeutic methods to treat this disease. Methods: Cell viability was determined by the Cell Counting Kit-8 (CCK-8) assay. Western blotting (WB) was used to detect the expression levels of apoptotic and endoribonuclease inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP-1) pathway-associated proteins. The induction of cell apoptosis was determined using flow cytometry. The expression levels of the oxidative stress indicators were measured by an enzyme-linked immunosorbent assay. Results: WB analysis and the CCK-8 assay demonstrated that trimethylamine-N-oxide (TMAO) decreased cell viability and facilitated apoptosis of MPC-83 cells in a dose-dependent manner. Furthermore, the induction of oxidative stress was assessed by evaluating the levels of specific markers, including hydrogen peroxide, reactive oxygen species, nitric oxide, and superoxide dismutase. The levels of the aforementioned markers were increased in the TMAO-treated group. Subsequently, the IRE1α/XBP-1 pathway-associated proteins were analyzed by WB analysis and the data demonstrated that the regulatory effects of TMAO on MPC-83 cells were meditated by the IRE1α/XBP-1 signaling pathway. Subsequently, rescue experiments were performed to further assess the effects of TMAO. Conclusion: The present study provides evidence on the application of TMAO as a potential diagnostic and therapeutic strategy for the therapeutic intervention of hyperlipidemic acute pancreatitis.
- Subjects
FLOW cytometry; ANIMAL experimentation; WESTERN immunoblotting; APOPTOSIS; SUPEROXIDE dismutase; AMINES; OXIDATIVE stress; CELLULAR signal transduction; RATS; HYPERLIPIDEMIA; CELL survival; ENZYME-linked immunosorbent assay; PANCREATITIS; CELL lines; REACTIVE oxygen species; NITRIC oxide; CARRIER proteins; DISEASE complications
- Publication
Saudi Journal of Gastroenterology, 2021, Vol 27, Issue 6, p361
- ISSN
1319-3767
- Publication type
Article
- DOI
10.4103/sjg.sjg_12_21