Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease

Yinchao Fang; Shanshan Ou; Tong Wu; Lingqi Zhou; Hai Tang; Mei Jiang; Jie Xu; Kaihua Guo

doi:10.7717/peerj.9308

Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease

PeerJ. 2020 Jun 8:8:e9308. doi: 10.7717/peerj.9308. eCollection 2020.

Authors

Yinchao Fang^#¹, Shanshan Ou^#^{1

2}, Tong Wu¹, Lingqi Zhou¹, Hai Tang³, Mei Jiang¹, Jie Xu^{1

4}, Kaihua Guo^{1

4}

Affiliations

¹ Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
² The 5th Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
³ Guangdong Jiangmen Chinese Medical College, Jiangmen, China.
⁴ Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

^# Contributed equally.

Abstract

Background & aims: Oxidative stress (OS) plays an important role in neurodegenerative diseases such as Alzheimer's disease (AD). Lycopene is a pigment with potent antioxidant and anti-tumor effects. However, its potential role in central nervous system is not well-defined. The aim of this study was to investigate the effect of lycopene on the cell model of AD and determine its underlying mechanisms.

Methods: M146L cell is a double-transfected (human APP gene and presenlin-1 gene) Chinese hamster ovary (CHO) cell line that overexpresses β -amyloid (Aβ) and is an ideal cell model for AD. We treated cells with lycopene, and observed the effect of lycopene on M146L cells.

Results: Oxidative stress and apoptosis in M146L cells were significantly higher than those in CHO cells, suggesting that Aβ induced OS and apoptosis. Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins. Additionally, lycopene inhibited β -secretase (BACE) activity in M146L cells. These results suggest that lycopene inhibits BACE activity and protects M146L cells from oxidative stress and apoptosis by activating the PI3K/Akt/Nrf2 pathway.

Conclusion: Lycopene possibly prevents Aβ-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells.

Keywords: Apoptosis; M146L cell; Oxidative stress; Lycopene.

Grants and funding

This research was supported by the National Natural Science Foundation of China (No. 31360258), the Science and Technology Planning Project of Guangdong Province (No. 2016A020215036), and the Natural Science Foundation of Guangdong Province (No. 2015A030313047, No. 2015A030313077, No. 2019A1515011184, and No. 2020A1515010012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.