Abstract
Oxidative stress plays an important role in the pathogenesis of cataracts. Small ubiquitin-like modifier (SUMO) proteins have great effects on cell stress response. Previous studies have shown that TP53INP1 can arrest cell growth and induce apoptosis by modulating p53 transcriptional activity and that both TP53INP1 and p53 are substrates of SUMOylation. However, no previous research has studied the effect of SUMOylation on the oxidative stress response in cataracts. This is the first study to investigate the effect of SUMOylation of TP53INP1 in oxidative stress-induced lens epithelial cell injury and age-related cataract formation. We found that the oxidative stress-induced endogenous SUMOylation of TP53INP1 promoted human lens epithelial cell (holed) apoptosis and regulated hLEC antioxidant effects by increasing the stability and transcription of TP53INP1 in age-related cataracts. SUMO-1, SUMOylation, and TP53INP1 were upregulated in lens tissues affected by age-related cataracts. A SUMO-1-specific protease, SENP1, acted as an oxidative stress-sensitive target gene in hLECs. This study identified for the first time that TP53INP1 can be SUMOylated in vivo, that the SUMOylation of TP53INP1 is induced by oxidative stress, and that SUMOylation/deSUMOylation can affect the stability and transcription of TP53INP1 in hLECs.
Highlights
Cataracts remain the leading cause of blindness worldwide [1]
Small ubiquitin-like modifier (SUMO) play an important role in the cell stress response, and many cell stresses lead to an increase in the formation of SUMO conjugates [16,17,18]
Compared with anterior lens capsules of the transparent lens group, Small ubiquitin-like modifier-1 (SUMO-1), TP53INP1, and p53 mRNA were significantly higher in the anterior lens capsules of age-related cataract patients (Figure 1(a))
Summary
Cataracts remain the leading cause of blindness worldwide [1]. the pathogenesis of cataract is still unclear. One universally recognized aspect of noncongenital cataract pathogenesis is that it is always preceded by lens epithelial cell apoptosis [2, 3]. Previous research has clearly demonstrated that various stimulating factors induce the production of reactive oxygen species in the lens and that these species are an important factor in the development of cataract [4, 5]. It has been demonstrated that cataract patients have significantly increased levels of reactive oxygen species in the anterior chamber and lens [6]. In vitro studies have further demonstrated that hydrogen peroxide equal to that in the lens of cataract patients caused lens epithelial cell apoptosis and lens opacity, changes similar to the pathological process in cataract patients [7, 8]. SUMOs play an important role in the cell stress response, and many cell stresses lead to an increase in the formation of SUMO conjugates [16,17,18]
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