NF-κB/Cartilage Acidic Protein 1 Promotes Ultraviolet B Irradiation-Induced Apoptosis of Human Lens Epithelial Cells

Abstract

The apoptosis of human lens epithelial cells (HLECs) is a characteristic change that occurs during the development of cataracts. Ultraviolet B (UVB) is known to induce the generation of reactive oxygen species (ROS) and apoptosis in HLECs, and thus cause cataracts. Previously, we reported the functions of cartilage acidic protein 1 (CRTAC1) in UVB-treated HLECs. However, the underlying mechanism was not known. In this study, we found that CRTAC1 expression and nuclear factor-kappa B (NF-κB) p65 nuclear translocation were elevated in capsule tissues of cataract patients in comparison with normal controls. The NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), alleviated UVB-induced apoptosis in HLECs; while activation of NF-κB suppressed the effects of the ROS inhibitor, N-acetyl-L-cysteine (NAC), on UVB-treated HLECs. The expression and promoter activity of CRTAC1 was inhibited by PDTC and NAC. Moreover, the suppressed effects of CRTAC1 knockdown on UVB-induced ROS generation, cell apoptosis, nuclear translocation of NF-κB p65, and p38 phosphorylation were attenuated by a p38 agonist. In contrast, the p38 inhibitor abolished the promotional effects of CRTAC1 overexpression on HLECs. Taken together, our results for the first time show that NF-κB is a potential transcription factor for CRTAC1. The regulatory network involving NF-κB, CRTAC1, and p38 may therefore play an important role in cataract formation.