Abstract

Ultraviolet-B (UVB) is a recognized risk factor for age-related cataract (ARC) and can cause various changes, including ubiquitination, in lens epithelial cells (LECs). However, the relationship between ubiquitination and ARC is unclear. Herein, we used UVB-irradiated human lens epithelial cell line (SRA01/04) representing the cell model of ARC to investigate the profile changes in the proteome and ubiquitome. A total of 552 differentially expressed proteins (DEPs) and 871 differentially ubiquitinated proteins (DUPs) were identified, and 9 ubiquitination motifs were found. Bioinformatics analysis revealed diverse pathways and biological processes of differential proteins and several DNA damage repair proteins that were potentially mediated via ubiquitin-proteasome pathway. We validated the decreased protein expression of DNA-directed RNA polymerase II subunit RPB2 (POLR2B) in both human cataract capsule tissues and UVB-treated SRA01/04 cells and found that treatment with proteasome inhibitor (MG-132) could reverse the protein level of POLR2B in UVB-irradiated SRA01/04 cells. Our data provide novel information regarding protein expressions and ubiquitination modifications in UVB-induced oxidative damage model. This study might offer a cell-level reference to further investigate the pathogenesis of ARC.

Highlights

  • Age-related cataract (ARC), defined as opacity of the crystalline lens in the eye, is the leading cause of severe visual impairment and blindness worldwide.[1]

  • Oxidative damage is a widely recognized risk factor for the pathogenesis of ARC, especially DNA oxidative damage, and timely and efficient repair of this damage is crucial to maintaining lens transparency

  • We attempted to use the box plot to indicate the relationship between differentially expressed proteins (DEPs) and differentially ubiquitinated proteins (DUPs), and the result showed no significant difference between groups (Supplemental Figure S1)

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Summary

Introduction

Age-related cataract (ARC), defined as opacity of the crystalline lens in the eye, is the leading cause of severe visual impairment and blindness worldwide.[1]. UVB-induced oxidative damage was found to cause accumulation of ubiquitinated proteins,[9] which prompted us to explore the potential pathogenesis of ARC

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