Journal
CELL CYCLE
Volume 22, Issue 12, Pages 1450-1462Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2023.2215084
Keywords
Cataract; ultraviolet B; reactive oxygen species; NF-kappa B; SVCT2; ascorbic acid
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Exposure to UVB radiation leads to the formation of cataracts by inducing excessive reactive oxygen species (ROS) and apoptosis in human lens epithelial cells (HLECs). Sodium-dependent Vitamin C transports-2 (SVCT2) is downregulated in UVB-treated HLECs, leading to increased ROS accumulation and apoptosis. The NF-κB/SVCT2/AsA regulatory pathway may provide therapeutic potential in UVB-induced cataract.
Ultraviolet B (UVB) exposure is reported to cause cataract formation by inducing excessive reactive oxygen species (ROS) and apoptosis in human lens epithelial cells (HLECs). Sodium-dependent Vitamin C transports-2 (SVCT2) is a ascorbic acid (AsA) transporter for that can protect cells and tissues from oxidative stress. Here, we focus on the functional characterization and mechanism analysis of SVCT2 in UVB-treated HLECs. The results showed a significant reduction of SVCT2 expression in HLECs treated with UVB. SVCT2 abated apoptosis and Bax expression and increased Bcl-2 expression. Moreover, SVCT2 decreased ROS accumulation and MDA level, but increased the activities of antioxidant enzymes (SOD and GSH-PX). NF-?B inhibitor (PDTC) alleviated ROS production and apoptosis, and promoted SVCT2 expression in UVB-treated HLECs. Additionally, ROS inhibitor (NAC) suppressed oxidative stress, apoptosis, and induced SVCT2 expression in UVB-treated HLECs, while these effects were significantly abated due to the activation of NF-?B signaling. Furthermore, SVCT2 facilitated C-14-AsA absorption in UVB-treated HLECs. Together, our findings demonstrated that UVB exposure-induced ROS generation, which further activated NF-?B signaling to down-regulate SVCT2 expression in HLECs. Then, downregulated SVCT2 promoted ROS accumulation and induced apoptosis by decreasing AsA uptake. Our data reveal a novel NF-?B/SVCT2/AsA regulatory pathway and suggest the therapeutic potential of SVCT2 in UVB-induced cataract.
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