HO‑1 alleviates cholesterol‑induced oxidative stress through activation of Nrf2/ERK and inhibition of PI3K/AKT pathways in endothelial cells

Jin,Xiaohan; Xu,Zhongwei; Fan,Rong; Wang,Chengyan; Ji,Wenjie; Ma,Yongqiang; Cai,Wei; Zhang,Yan; Yang,Ning; Zou,Shuang; Zhou,Xin; Li,Yuming

doi:10.3892/mmr.2017.6962

HO‑1 alleviates cholesterol‑induced oxidative stress through activation of Nrf2/ERK and inhibition of PI3K/AKT pathways in endothelial cells

Authors:
- Xiaohan Jin
- Zhongwei Xu
- Rong Fan
- Chengyan Wang
- Wenjie Ji
- Yongqiang Ma
- Wei Cai
- Yan Zhang
- Ning Yang
- Shuang Zou
- Xin Zhou
- Yuming Li
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Affiliations: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of People's Armed Police Force, Tianjin 300162, P.R. China, Central Laboratory, Logistics University of People's Armed Police Force, Tianjin 300309, P.R. China
Published online on: July 13, 2017 https://doi.org/10.3892/mmr.2017.6962
Pages: 3519-3527

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Abstract

Heme oxygenase‑1 (HO‑1), as an inducible and cytoprotective enzyme, has a protective effect against cellular oxidative stress. In the present study, cholesterol was used to induce lipid overload and increase reactive oxygen species (ROS), leading to oxidative stress in EA.hy926 cells. In the present study, western blotting and immunofluorescence analysis were used to detect the expression level of important molecules in the metabolism process of cholesterol. It was confirmed that cholesterol stimulation upregulated the expression of HO‑1 in a time‑dependent manner via the activation and translocation of nuclear factor erythroid 2‑related factor 2 (Nrf2), activation of the mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling pathway and increasing intercellular Ca2+ ([Ca2+]i) concentration. The results showed that increasing the expression of HO‑1 decreased activation of the phosphoinositide 3‑kinase (PI3K)/AKT signaling pathway and inhibited the expression of c‑Myc. It was confirmed that cholesterol‑mediated oxidative damage in vascular endothelial cells induced an increase in the expression of HO‑1 via the activation of Nrf2 and the MAPK/ERK signaling pathway, and increasing the [Ca2+]i concentration. The overexpression of HO‑1 alleviated oxidative damage through inhibition of the PI3K/AKT signaling pathway and downregulation of the expression of c‑Myc.

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