Activation of the Nrf2/HO-1 Signaling Pathway Contributes to the Protective Effects of Sargassum serratifolium Extract against Oxidative Stress-Induced DNA Damage and Apoptosis in SW1353 Human Chondrocytes.

Cheol Park,Soon Shin,Gi-Young Kim,Eui Park,Hee-Jae Cha,Suhkmann Kim,Yung Choi,You-Jin Jeon,Heui-Soo Kim,Su Hong,Min Han,Dae-Sung Lee

doi:10.3390/ijerph15061173

Abstract

Oxidative stress in chondrocytes plays a critical role in the pathogenesis of osteoarthritis as an important cause of articular cartilage degradation. Sargassum serratifolium C. Agardh, a marine brown algae, is known to have potent antioxidant activity. Nevertheless, no study has been conducted yet on the protective efficacy against oxidative stress in chondrocytes. Therefore, the aim of the current study is to investigate the mechanism of the antioxidative effect of ethanol extract of S. serratifolium (EESS) on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in SW1353 human chondrocytes. For this purpose, SW1353 cells exposed to H2O2 in the presence or absence of EESS were applied to cell viability assay, comet assay, immunoblotting and flow cytometry analyses. Our results showed that EESS effectively attenuated H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. EESS also weakened the mitochondria membrane permeabilization by H2O2, and recovered H2O2-induced decreased expression of anti-apoptotic Bcl-2 and pro-caspase-3, and degradation of poly (ADP-ribose) polymerase. In addition, EESS increased not only expression, but also phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2), and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, but decreased the expression of kelch-like ECH-associated protein-1; however, the inhibition of HO-1 activity by zinc protoporphyrin abolished the antioxidant potential induced by EESS against H2O2-mediated oxidative stress. Therefore, the results of this study suggest that the antioxidant efficacy of EESS in chondrocytes is at least involved in the Nrf2/HO-1 signaling pathway-dependent mechanism.

Highlights

When chondrocytes are damaged by a variety of oxidative stimuli, the production of inflammatory factors and the activity of proteolytic enzymes are increased, and the initiation of apoptosis with increased generation of reactive oxygen species (ROS) is promoted [1,2]
We investigated the protective effect of ethanol extract of S. serratifolium (EESS) on DNA damage and apoptosis in SW1353 human chondrocytes by mimicking in vitro oxidation using pro-oxidant agent and its related mechanism, especially the expression of nuclear transcription factor erythroid-2-like factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway
Cytotoxicity inconditions, SW1353 Chondrocytes concentrations of EESS, and cell viability was examined by MTT assay

Summary

Introduction

When chondrocytes are damaged by a variety of oxidative stimuli, the production of inflammatory factors and the activity of proteolytic enzymes are increased, and the initiation of apoptosis with increased generation of reactive oxygen species (ROS) is promoted [1,2]. Activation of proteolytic caspase cascade, as well as mitochondrial dysfunction, plays an important role in inducing the apoptosis of chondrocytes by oxidative stress [3,4]. To protect cartilage cells, the establishment of appropriate antioxidant strategies and discovery of antioxidants to protect against oxidative stress are required. Most cells, including chondrocytes, have endogenous defense strategies to eliminate the damage caused by excessive ROS production. The nuclear transcription factor erythroid-2-like factor 2 (Nrf2)/antioxidant response element (ARE) signaling is one of the critical antioxidant systems involved in the maintenance of the redox state for the defense of intracellular oxidative stress [7,8]

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