SUMOylation Evoked by Oxidative Stress Reduced Lens Epithelial Cell Antioxidant Functions by Increasing the Stability and Transcription of TP53INP1 in Age-Related Cataracts

Lü, Bo; Christensen, Ian T.; Yu, Tao; Wang, Chunxia; Yan, Qichang; Wang, Xinling

doi:10.1155/2019/7898069

Cited by 16 publications

(7 citation statements)

References 58 publications

(58 reference statements)

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“…Also, mutant Peroxiredoxin-6 at its SUMO1 sites could gain protective functions by maintaining its integrity and activity in epithelial cells of the aging human lens. Recently, SUMOylation has inspired an increasing number of researchers to explore the different target proteins and roles in the development of ocular disease treatments 24,52 . Currently, we focused on p48 PAX6 SUMOylation, including major sites, and SENP1-mediated de-SUMOylation improves the stability of PAX6 and amplifies the protective effects of PAX6 on corneal endothelial injuries.…”

Section: Discussionmentioning

confidence: 99%

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Zhang

Yan

et al. 2020

Cell Death Dis

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Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits corneal endothelial defects. However, the effects of PAX6 protein involved in corneal endothelial wound process are still unknown. Here, we found the upregulated protein levels of PAX6 in human corneal endothelial monolayer after injury; the expression of PAX6 also increased in murine and rat corneal endothelium injury models. Enforced PAX6 expression could alleviate the damages to CECs via regulating permeability by prompting cellular tight junction. In addition, SUMOylation mainly happened on both K53 and K89 residues of 48-kD PAX6 (the longest and main isoform expressed in cornea), and de-SUMOylation promoted the stability of PAX6 protein in vitro. In CECs of SENP1 +/− mice, increased SUMOylation levels leading to instability and low expression of PAX6, delayed the repair of CECs after injury. Furthermore, overexpression of PAX6 accelerated the rate of corneal endothelial repair of SENP1 +/− mice. Our findings indicate that SENP1mediated de-SUMOylation improving the stability of PAX6, amplifies the protective effects of PAX6 on corneal endothelial injuries, highlighting potentials of PAX6 and/or SUMOylation to be used as a treatment target for corneal endothelial disorders.

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Section: Discussionmentioning

confidence: 99%

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Zhang

Yan

et al. 2020

Cell Death Dis

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“…[3][4][5] Studies have confirmed that cataracts are directly related to the apoptosis of LECs caused by oxygen free radicals. 6,7 Thus, it is important to explore antioxidant drugs that can prevent the formation and development of cataracts.…”

Section: Introductionmentioning

confidence: 99%

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

Ran¹,

Liu²,

Wu³

2021

Adv Clin Exp Med

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Background.Oxidative stress has been reported to be an early factor in the development of cataracts. Echinatin (Ech) is an active ingredient of licorice that exhibits antioxidant effects. Objectives.To investigate the effects of Ech on oxidative stress-induced lens epithelial cell (LEC) damage. Materials and methods.Human lens epithelial B3 cells (HLECs) were exposed to hydrogen peroxide (H 2 O 2 ) and were pretreated with or without Ech. For rescue experiments, ML385, an inhibitor of the Nrf2 pathway, was added into the medium.Results. Echinatin reversed the H 2 O 2 -induced reduction of cell viability in B3 cells. Additionally, H 2 O 2 induced oxidative stress, evidenced by an increase of reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and a decrease in superoxide dismutase (SOD) and catalase (CAT) levels, which could be abolished by Ech. Echinatin treatment also reduced HLEC apoptosis induced by H 2 O 2 . In addition, Ech pretreatment promoted Bcl-2 expression, and suppressed Bax and caspase-3 expression levels, in H 2 O 2 -treated B3 cells. Moreover, H 2 O 2 significantly reduced Nrf2 nuclear localization, as well as HO-1 and NQO1 expression, which could be reversed by Ech. Inhibition of Nrf2 by ML385 aggravated H 2 O 2 -induced oxidative damage and apoptosis in HLECs, and the protective effects of Ech on H 2 O 2 -induced oxidative damage and apoptosis could be restored by ML385. Conclusions.Echinatin mitigates H 2 O 2 -induced oxidative damage and apoptosis in HLECs via the Nrf2/HO-1 pathway, suggesting that Ech may be a potential drug for the treatment of cataracts.

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“…Studies have been revealed that antioxidant agents prevent the generation of free radicals that participate in the process of cataract formation (Chang et al, 2013;Abbas and Hussain, 2017). Exposure to environmental stresses (lead to elevated oxidative stress) threatens the eye health (Lu et al, 2019). Oxidative damage in the eye lens is responsible for many types of cataract (Varma et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

The association between healthy eating index and serum antioxidant indices in patients with different degrees of cataract compared to healthy subjects: a case-control study

Heidari

Jabbari

Babashahi

et al. 2020

NFS

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Purpose Studies conducted on association between diet and cataract, found conflicting results. This paper aims to investigate the association between healthy eating index (HEI) and serum antioxidant and oxidant indices in patients with different degrees of cataract compared to the healthy subjects. Design/methodology/approach Ninety volunteers (aged > 50 years) were divided into the cataract (n = 45) and healthy control (n = 45) groups in this case-control study. Anthropometric variables, HEI score, serum total oxidant capacity (TOC) and total antioxidant capacity (TAC), blood pressure, physical activity and stress measurements were done for all participants. Findings There was a significant difference in stress level between subgroup of first-degree cataract and healthy controls (16.6 ± 2.3 vs 42.5 ± 29.0, p < 0.001) as well as third-degree cataract (16.6 ± 2.3 vs 75.2 ± 22.6, p < 0.001). Serum TAC was significantly higher in healthy people compared to the first-degree (1.2 ± 0.2 vs 1 ± 0.2, p = 0.002) and third-degree cataract patients (1.2 ± 0.2 vs 1.0 ± 0.2, p = 0.013). Also, serum TOC was significantly lower in healthy controls compared to the first-degree (8.2 ± 1.1 vs 9.2 ± 1.0, p = 0.006) and third-degree cataract patients (8.2 ± 1.1 vs 9.1 ± 1.2, p = 0.015). There was a significant direct correlation between moderation (r = 0.61, p = 0.019) and total score of HEI (r = 0.57, p = 0.031) with serum TAC only in the first-degree cataract patients. Also there was a significant negative correlation between moderation score of HEI with serum TOC in the first-degree cataract patients (r = −0.60, p = 0.025), and there was a significant negative correlation between moderation (r = −0.36, p = 0.017) and total score (r=−0.35, p = 0.021) of HEI and TOC in the total cataract patients. Originality/value To the best of the authors’ knowledge, this is the first study on the assessment of the relationship between components of HEI and serum antioxidant indicators in different types of cataract compared to healthy individuals. It could be a start point for more detailed and large-scaled studies, even intervention studies, in this field.

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SUMOylation Evoked by Oxidative Stress Reduced Lens Epithelial Cell Antioxidant Functions by Increasing the Stability and Transcription of TP53INP1 in Age-Related Cataracts

Cited by 16 publications

References 58 publications

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

PAX6, modified by SUMOylation, plays a protective role in corneal endothelial injury

Echinatin mitigates H2O2-induced oxidative damage and apoptosis in lens epithelial cells via the Nrf2/HO-1 pathway

The association between healthy eating index and serum antioxidant indices in patients with different degrees of cataract compared to healthy subjects: a case-control study

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