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Alcohol Aggravates Acute Pancreatitis by Impairing Autophagic Flux Through Activation of AMPK Signaling Pathway

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Abstract

Objective

Alcohol consumption is always the main cause of acute pancreatitis (AP). It has been reported that alcohol exerts direct damage to the pancreas. However, the specific role of alcohol during AP needs to be investigated. This study aims to examine the effects of alcohol in cerulein-induced AP and the role of the AMPK pathway.

Methods

Human subjects from operations, cerulein-induced AP rat, and cerulein-stimulated AR42J cell line were enrolled in this study. Electron microscopy was employed for observation of cell morphology, immunohistochemistry for identification of cells, ELISA for detection of inflammation factors, Annexin V/PI double staining for evaluation of cell apoptosis, immunofluorescence for assessment of autophagic flux, oil red O staining for examination of lipid droplet accumulation, and Western blot for measurement of expressions of proteins related to autophagy, apoptosis, and AMPK signal pathway. PI3K inhibitor 3-MA and AMPK inhibitor BML-275 were utilized for investigation of the relationship between impaired autophagic flux and the AMPK pathway by inhibiting or stimulating the formation of autophagosome.

Results

Alcohol consumption caused lipid droplet accumulation in the pancreas, and it also activated AMPK signaling pathway, thus aggravating the autophagic flux during AP. Alcohol up-regulated the expressions of anti-apoptotic proteins during the induction of AP to inhibit cell apoptosis and enhance cell necrosis. Inhibition of autophagosome formation by AMPK inhibitor BML-275 ameliorated the decreased cell viability caused by alcohol and cerulein in vitro.

Conclusion

Alcohol aggravates AP progression by impairing autophagic flux and enhancing cell autophagy through the AMPK signaling pathway.

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Acknowledgment

Thanks for all the supports and contributions of participators.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 8170031418), Heilongjiang Postdoctoral Foundation (No. LBH-18181) and China Postdoctoral Science Foundation (No. 2019M651302).

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Authors and Affiliations

  1. Second Colorectal Surgery Department, Harbin Medical University Tumor Hospital, No. 150, Haping Road, Nangang District, Harbin, 150001, Heilongjiang, People’s Republic of China

    Jiachen Lv & Jinxue Tong

  2. Breast Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, People’s Republic of China

    Liang Ji

  3. Pancreatic and Biliary Surgery Department, The First Affiliated Hospital of Harbin Medical University, No. 25, Youzheng Street, Nangang District, Harbin, 150001, Heilongjiang, People’s Republic of China

    Gang Wang & Bei Sun

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  1. Jiachen Lv
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Correspondence to Jinxue Tong.

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Lv, J., Ji, L., Wang, G. et al. Alcohol Aggravates Acute Pancreatitis by Impairing Autophagic Flux Through Activation of AMPK Signaling Pathway. Dig Dis Sci 67, 524–535 (2022). https://doi.org/10.1007/s10620-021-06870-1

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  • DOI: https://doi.org/10.1007/s10620-021-06870-1

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