Catalpol Protects ARPE-19 Cells against Oxidative Stress via Activation of the Keap1/Nrf2/ARE Pathway.

Longtai You,Xiaoxv Dong,Xingbin Yin,Mengru Cai,Jing Liu,Hulinyue Peng,Jian Ni,Zhiqin Zhang,Yu Yao,Huimin Wu,Jie Bai

doi:10.3390/cells10102635

Longtai You, Xiaoxv Dong + Show 9 more

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https://doi.org/10.3390/cells10102635

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Journal: Cells	Publication Date: Oct 2, 2021
Citations: 24	License type: CC BY 4.0

Affiliation: Beijing University of Chinese Medicine

Abstract

Oxidative damage to retinal pigment epithelial (RPE) has been identified as one of the major regulatory factors in the pathogenesis of age-related macular degeneration (AMD). Catalpol is an iridoid glucoside compound that has been found to possess potential antioxidant activity. In the present study, we aimed to investigate the protective effect of catalpol on RPE cells under oxidative stress and to elucidate the potential molecular mechanism involved. We found that catalpol significantly attenuated hydrogen peroxide (H2O2)-induced cytotoxicity, G0/G1 phase cell cycle arrest, and apoptosis in RPE cells. The overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA) stimulated by oxidative stress and the corresponding reductions in antioxidant glutathione (GSH) and superoxide dismutase (SOD) levels were largely reversed by catalpol pretreatment. Moreover, catalpol pretreatment markedly activated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its downstream antioxidant enzymes, catalase (CAT), heme oxygenase-1 (HO-1), and NADPH dehydrogenase (NQO1). It also increased the expression levels of cyclin E, Bcl-2, cyclin A, and cyclin-dependent kinase 2 (CDK2) and decreased the expression levels of Bax, Fas, cleaved PARP, p-p53, and p21 cleaved caspase-3, 8, and 9. The oxidative stress-induced formation of the Keap1/Nrf2 complex in the cytoplasm was significantly blocked by catalpol pretreatment. These results indicate that catalpol protected RPE cells from oxidative stress through a mechanism involving the activation of the Keap1/Nrf2/ARE pathways and the inactivation of oxidative stress-mediated pathways of apoptosis.

Highlights

Age-related macular degeneration (AMD) is an irreversible visual impairment associated disease prevalent in the elderly population around the world
Compared with the H2 O2 -treated group, catalpol pretreatment increased the viability of ARPE-19 cells in a dose-dependent manner (Figure 1c)
Previous studies have shown that oxidative stress-induced mitochondrial dysfunction in retinal pigment epithelial (RPE) cells and activation of its downstream apoptotic pathway have been identified as key factors in the pathogenesis of early AMD [6,7,8,9,10]; we further investigated the mechanism of the anti-apoptotic effect of catalpol under oxidative stress

Summary

Introduction

Age-related macular degeneration (AMD) is an irreversible visual impairment associated disease prevalent in the elderly population around the world. Cell dysfunction and apoptosis have been identified as crucial factors involved in the pathogenesis of early AMD [6]. Oxidative stress damage leads to mitochondrial dysfunction and the production of abnormal lipid molecules in RPE cells. These products accumulate inside the Bruch’s membrane, leading to the formation of drusen which is one of the hallmarks of early AMD [9,10]. A growing corpus of evidence suggests that antioxidants, by inhibiting the production of ROS, protect RPE cells from oxidative stress, thereby playing a key therapeutic role in early AMD [11].

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