Attenuation of the Na/K‑ATPase/Src/ROS amplification signaling pathway by astaxanthin ameliorates myocardial cell oxidative stress injury

Qu,Xuefeng; Zhang,Zhouyi; Hu,Wenli; Lou,Minhan; Zhai,Bingzhong; Mei,Song; Hu,Zhihang; Zhang,Lijing; Liu,Dongying; Liu,Zhen; Chen,Jianguo; Wang,Yin

doi:10.3892/mmr.2020.11613

Attenuation of the Na/K‑ATPase/Src/ROS amplification signaling pathway by astaxanthin ameliorates myocardial cell oxidative stress injury

Authors:
- Xuefeng Qu
- Zhouyi Zhang
- Wenli Hu
- Minhan Lou
- Bingzhong Zhai
- Song Mei
- Zhihang Hu
- Lijing Zhang
- Dongying Liu
- Zhen Liu
- Jianguo Chen
- Yin Wang
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Affiliations: Zhejiang Academy of Medical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 310013, P.R. China
Published online on: October 19, 2020 https://doi.org/10.3892/mmr.2020.11613
Pages: 5125-5134
Copyright: © Qu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The 3S, 3'S‑ASTaxanthin (3S, 3'S‑AST) isomer has strong antioxidant activity; however, its protective roles and potential mechanisms against oxidative stress damage in cardiomyocytes have not been investigated. Na+/K+‑ATPase (NKA)/Src signal activation has an important role in increasing reactive oxygen species (ROS) production. The aim of the present study was to investigate the protective effects and mechanism of 3S, 3'S‑AST on hydrogen peroxide (H2O2)‑induced oxidative stress injury in H9c2 myocardial cells. The protective effects of 3S, 3'S‑AST on H2O2‑induced H9c2 cell injury was observed by measuring lactate dehydrogenase and creatine kinase myocardial band content, cell viability and nuclear morphology. The antioxidant effect was investigated by analyzing ROS accumulation and malondialdehyde, glutathione (GSH) peroxidase, GSH and glutathione reductase activity levels. The protein expression levels of Bax, Bcl‑2, caspase‑3 and cleaved caspase‑3 were analyzed using western blotting to determine cardiomyocyte apoptosis. Western blot analysis of the phosphorylation levels of Src and Erk1/2 were also performed to elucidate the molecular mechanism involved. The results showed that 3S, 3'S‑AST reduced the release of LDH and promoted cell viability, and attenuated ROS accumulation and cell apoptosis induced by H2O2. Furthermore, 3S, 3'S‑AST also restored apoptosis‑related Bax and Bcl‑2 protein expression levels in H2O2‑treated H9c2 cells. The phosphorylation levels of Src and Erk1/2 were significantly higher in the H2O2 treatment group, whereas 3S, 3'S‑AST pretreatment significantly decreased the levels of phosphorylated (p)‑Src and p‑ERK1/2. The results provided evidence that 3S, 3'S‑AST exhibited a cardioprotective effect against oxidative stress injury by attenuating NKA/Src/Erk1/2‑modulated ROS amplification.

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