Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment
Cataracts are a serious complication of diabetes. In long-term hyperglycemia, intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and reactive oxygen species (ROS) are increased. The apoptosis of lens epithelial cells plays a key role in th...
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2022-04-01
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author | Linghui Chen Yanzhuo Chen Wen Ding Tao Zhan Jie Zhu Lesha Zhang Han Wang Bing Shen Yong Wang |
author_facet | Linghui Chen Yanzhuo Chen Wen Ding Tao Zhan Jie Zhu Lesha Zhang Han Wang Bing Shen Yong Wang |
author_sort | Linghui Chen |
collection | DOAJ |
description | Cataracts are a serious complication of diabetes. In long-term hyperglycemia, intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and reactive oxygen species (ROS) are increased. The apoptosis of lens epithelial cells plays a key role in the development of cataract. We investigated a potential role for transient receptor potential vanilloid 2 (TRPV2) in the development of diabetic cataracts. Immunohistochemical and Western blotting analyses showed that TRPV2 expression levels were significantly increased in the lens epithelial cells of patients with diabetic cataracts as compared with senile cataract, as well as in both a human lens epithelial cell line (HLEpiC) and primary rat lens epithelial cells (RLEpiCs) cultured under high-glucose conditions. The [Ca<sup>2+</sup>]<sub>i</sub> increase evoked by a TRPV2 channel agonist was significantly enhanced in both HLEpiCs and RLEpiCs cultured in high-glucose media. This enhancement was blocked by the TRPV2 nonspecific inhibitor ruthenium red and by TRPV2-specific small interfering (si)RNA transfection. Culturing HLEpiCs or RLEpiCs for seven days in high glucose significantly increased apoptosis, which was inhibited by TRPV2-specific siRNA transfection. In addition, ROS inhibitor significantly suppressed the ROS-induced increase of TRPV2-mediated Ca<sup>2+</sup> signal and apoptosis under high-glucose conditions. These findings suggest a mechanism underlying high-glucose–induced apoptosis of lens epithelial cells, and offer a potential target for developing new therapeutic options for diabetes-related cataracts. |
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spelling | doaj.art-a6513a5466f344cebfa90882a6b4cdb72023-11-30T23:04:47ZengMDPI AGCells2073-44092022-04-01117119610.3390/cells11071196Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose EnvironmentLinghui Chen0Yanzhuo Chen1Wen Ding2Tao Zhan3Jie Zhu4Lesha Zhang5Han Wang6Bing Shen7Yong Wang8Department of Ophthalmology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaDepartment of Ophthalmology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaDepartment of Ophthalmology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaDepartment of Ophthalmology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaCataracts are a serious complication of diabetes. In long-term hyperglycemia, intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) and reactive oxygen species (ROS) are increased. The apoptosis of lens epithelial cells plays a key role in the development of cataract. We investigated a potential role for transient receptor potential vanilloid 2 (TRPV2) in the development of diabetic cataracts. Immunohistochemical and Western blotting analyses showed that TRPV2 expression levels were significantly increased in the lens epithelial cells of patients with diabetic cataracts as compared with senile cataract, as well as in both a human lens epithelial cell line (HLEpiC) and primary rat lens epithelial cells (RLEpiCs) cultured under high-glucose conditions. The [Ca<sup>2+</sup>]<sub>i</sub> increase evoked by a TRPV2 channel agonist was significantly enhanced in both HLEpiCs and RLEpiCs cultured in high-glucose media. This enhancement was blocked by the TRPV2 nonspecific inhibitor ruthenium red and by TRPV2-specific small interfering (si)RNA transfection. Culturing HLEpiCs or RLEpiCs for seven days in high glucose significantly increased apoptosis, which was inhibited by TRPV2-specific siRNA transfection. In addition, ROS inhibitor significantly suppressed the ROS-induced increase of TRPV2-mediated Ca<sup>2+</sup> signal and apoptosis under high-glucose conditions. These findings suggest a mechanism underlying high-glucose–induced apoptosis of lens epithelial cells, and offer a potential target for developing new therapeutic options for diabetes-related cataracts.https://www.mdpi.com/2073-4409/11/7/1196TRPV2diabetic cataractapoptosishuman lens epithelial cell |
spellingShingle | Linghui Chen Yanzhuo Chen Wen Ding Tao Zhan Jie Zhu Lesha Zhang Han Wang Bing Shen Yong Wang Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment Cells TRPV2 diabetic cataract apoptosis human lens epithelial cell |
title | Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment |
title_full | Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment |
title_fullStr | Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment |
title_full_unstemmed | Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment |
title_short | Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment |
title_sort | oxidative stress induced trpv2 expression increase is involved in diabetic cataracts and apoptosis of lens epithelial cells in a high glucose environment |
topic | TRPV2 diabetic cataract apoptosis human lens epithelial cell |
url | https://www.mdpi.com/2073-4409/11/7/1196 |
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