APPL1 ameliorates myocardial ischemia‑reperfusion injury by regulating the AMPK signaling pathway

Cen,Yunguang; Liao,Wei; Wang,Taihao; Zhang,Daimin

doi:10.3892/etm.2021.11080

APPL1 ameliorates myocardial ischemia‑reperfusion injury by regulating the AMPK signaling pathway

Authors:
- Yunguang Cen
- Wei Liao
- Taihao Wang
- Daimin Zhang
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Affiliations: Department of Geriatric Center, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, P.R. China, Department of Medical Ultrasonics, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan 570311, P.R. China, Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China
Published online on: December 17, 2021 https://doi.org/10.3892/etm.2021.11080
Article Number: 157
Copyright: © Cen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Myocardial ischemia‑reperfusion injury results in elevated reactive oxygen species (ROS) production and causes oxidative stress damage. Therefore, the current study aimed to investigate whether adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) could induce the expression of antioxidant enzymes through AMP‑activated protein kinase (AMPK) signaling in order to alleviate the injury caused by ischemia/hypoxia‑reperfusion. Following induction of hypoxia‑reoxygenation (H/R) injury in H9c2 cells, the liver kinase B1 (LKB1)/AMPK/acetyl‑CoA carboxylase α (ACC) signaling pathway was investigated using western blot analysis, along with the detection of superoxide dismutase (SOD)2 and SOD3 expression. Additionally, cell viability was detected using a Cell Counting Kit‑8 assay and ROS production was analyzed using ROS staining, whereas the expression levels of inflammatory mediators (TNF‑α, monocyte chemoattractant protein 1 and IL‑1β), apoptosis mediators [cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase and Bcl‑2] and nuclear factor erythroid 2‑related factor 2 signaling pathway‑related proteins were detected via western blot analysis following overexpression of APPL1 alone or in combination with compound C treatment (an AMPK inhibitor). The results indicated that H/R induction upregulated the phosphorylation levels of LKB1, AMPK and ACC, and decreased the expression levels of APPL1 and SOD enzyme activities. APPL1 overexpression increased the phosphorylation levels of LKB1, AMPK and ACC, SOD enzyme activity and cell viability whereas the expression levels of proinflammatory mediators and proapoptotic mediators, and the levels of ROS production were markedly decreased when compared with H/R group with empty plasmid transfection. APPL overexpression‑mediated effects were significantly abrogated by compound C. Taken together, the data indicated that APPL1 inhibited ROS production and H/R‑induced myocardial injury via the AMPK signaling pathway. Therefore, APPL1 may serve as a potential therapeutic target for myocardial H/R injury.

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