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ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells

  • Authors:
    • Lingfeng Jiang
    • Wenkai Zhou
    • Bo Lu
    • Qichang Yan
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Fourth Affiliated Hospital of China Medical University, Ophthalmology Hospital of China Medical University, Key Laboratory of Lens in Liaoning Province, Shenyang, Liaoning 110005, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4307-4319
    |
    Published online on: September 9, 2020
       https://doi.org/10.3892/mmr.2020.11499
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Abstract

Thioredoxin (Trx) is an important protein that controls oxidative damage in almost all eukaryotic cells. Trx interaction protein (Txnip) has been reported to negatively regulate the bioavailability of Trx and inhibit its biological function. The E3 ubiquitin ligase ITCH can specifically degrade Txnip via ubiquitination. The apoptosis of human lens epithelial cells (HLECs), which are highly sensitive to redox caused by oxidative stress, is a significant factor for the development of sugar cataract in a high‑glucose environment. However, whether Trx, Txnip and ITCH contribute to the progression of sugar cataracts and the underlying mechanisms remain unknown, and thus, identifying these were the aims of the present study. The present results suggested that the expression levels of Trx, Txnip and ITCH in HLECs cultured with different glucose concentrations were detected by reverse transcription‑quantitative PCR and western blotting, and the apoptotic rate of the cells was detected by flow cytometry and superoxide detection assay. The interaction between ITCH and Txnip was determined by co‑localization immunofluorescence and co‑immunoprecipitation. In addition, a vector and small interfering RNA of ITCH were transfected to overexpress and knockdown ITCH, respectively, to alter the expression of downstream proteins and cell apoptosis. It was found that Txnip was highly expressed in cultured HLECs in high‑glucose environment, and the antioxidative function of Trx was restricted and suppressed, thus promoting apoptosis. The overexpression of ITCH increased the expression of Trx and decreased oxidative stress and apoptosis by decreasing Txnip in cultured HLECs, while downregulation of ITCH significantly decreased the expression of Trx and enhanced oxidative stress and apoptosis. Therefore, the present results indicated that ITCH could regulate the apoptosis of HLECs that were cultured in high‑glucose concentration and that it may be a treatment target for sugar cataract.
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Copy and paste a formatted citation
Spandidos Publications style
Jiang L, Zhou W, Lu B and Yan Q: ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells. Mol Med Rep 22: 4307-4319, 2020.
APA
Jiang, L., Zhou, W., Lu, B., & Yan, Q. (2020). ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells. Molecular Medicine Reports, 22, 4307-4319. https://doi.org/10.3892/mmr.2020.11499
MLA
Jiang, L., Zhou, W., Lu, B., Yan, Q."ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells". Molecular Medicine Reports 22.5 (2020): 4307-4319.
Chicago
Jiang, L., Zhou, W., Lu, B., Yan, Q."ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells". Molecular Medicine Reports 22, no. 5 (2020): 4307-4319. https://doi.org/10.3892/mmr.2020.11499
Copy and paste a formatted citation
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Spandidos Publications style
Jiang L, Zhou W, Lu B and Yan Q: ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells. Mol Med Rep 22: 4307-4319, 2020.
APA
Jiang, L., Zhou, W., Lu, B., & Yan, Q. (2020). ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells. Molecular Medicine Reports, 22, 4307-4319. https://doi.org/10.3892/mmr.2020.11499
MLA
Jiang, L., Zhou, W., Lu, B., Yan, Q."ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells". Molecular Medicine Reports 22.5 (2020): 4307-4319.
Chicago
Jiang, L., Zhou, W., Lu, B., Yan, Q."ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells". Molecular Medicine Reports 22, no. 5 (2020): 4307-4319. https://doi.org/10.3892/mmr.2020.11499
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