Adenosine A<sub>1</sub> receptor agonism protection mechanism in intestinal ischemia/reperfusion injury via activation of PI3K/Akt signaling

Xu,Qian; Mao,Zun; Yun,Yi

doi:10.3892/etm.2022.11740

Adenosine A₁ receptor agonism protection mechanism in intestinal ischemia/reperfusion injury via activation of PI3K/Akt signaling

Authors:
- Qian Xu
- Zun Mao
- Yi Yun
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Affiliations: Department of Pharmacy, Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu 223800, P.R. China, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China
Published online on: November 30, 2022 https://doi.org/10.3892/etm.2022.11740
Article Number: 41
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intestinal ischemia/reperfusion (I/R) injury is a common clinical problem with a high mortality rate, resulting from loss of blood flow to an intestinal segment. Adenosine serves a protective role in intestinal I/R injury; however, its potential mechanism is not completely understood. The present study aimed to investigate the protective effects of adenosine A₁ receptor (A₁R) agonists CPA and LUF6941 and whether their mechanisms are associated with the PI3K/Akt signaling pathway. To simulate intestinal I/R injury, a cell oxygen‑glucose deprivation/reoxygenation (OGD/R) model was established and the human colon cancer cell line (Caco‑2) was incubated with A₁R agonists before OGD/R treatment. The viability of Caco‑2 cells was detected by PI and Cell Counting Kit‑8 assay, apoptosis was detected using flow cytometry and western blotting was used to analyze protein expression levels of PI3K, Akt and p53 in Caco‑2 cells. A₁R agonist pretreatment protected Caco‑2 cells against OGD/R‑induced cell damage and activated PI3K/Akt signaling. Additionally, apoptosis was inhibited by downregulating phosphorylation of p53 protein, as evidenced by increased cell viability. These findings suggested that A₁R agonists decreased OGD/R damage in Caco‑2 cells, which may be due to their anti‑apoptotic effects and activation of the PI3K/Akt/p53 signal pathway.

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