Oxidative Stress-Induced TRPV2 Expression Increase Is Involved in Diabetic Cataracts and Apoptosis of Lens Epithelial Cells in a High-Glucose Environment.
Linghui ChenYanzhuo ChenWen DingTao ZhanJie ZhuLesha ZhangHan WangBing ShenYong WangPublished in: Cells (2022)
Cataracts are a serious complication of diabetes. In long-term hyperglycemia, intracellular Ca 2+ concentration ([Ca 2+ ] i ) 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 2+ ] i 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 2+ 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.
Keyphrases
- high glucose
- endothelial cells
- endoplasmic reticulum stress
- reactive oxygen species
- oxidative stress
- induced apoptosis
- cell death
- neuropathic pain
- type diabetes
- cataract surgery
- cell cycle arrest
- dna damage
- cardiovascular disease
- poor prognosis
- wound healing
- glycemic control
- protein kinase
- binding protein
- high resolution
- mass spectrometry
- signaling pathway
- skeletal muscle
- weight loss
- south africa
- diabetic rats
- cell proliferation
- brain injury
- atomic force microscopy