Abstract
Purpose: :
UV irradiation is known to be associated with cataract formation likely via damaging a variety of cellular components. Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion, which plays important rules in the remodeling of lens capsule, cell–cell interactions and cell migration, and possibly cataract formation. Less is known about the effect of UV irradiation on desmosomal components.
Methods: :
Cultured human lens cells were used. Western blot analysis, FACS analysis and Immunofluorescence were applied in the study.
Results: :
In cultured human lens cells, we observed that UV induced desmoglein–2 (Dsg–2) degradation in a time and dose dependent manner. We also found that H2O2 induced desmoglein–2 degradation in a similar pattern. FACS analysis results indicated that UV irradiation induced reactive oxygen species (ROS) generation in a time and dose dependent manner. NAC partially blocked UV–induced degradation of Dsg–2. To investigate the mechanism of UV–induced ROS generation which may lead to Dsg–2 degradation, we examined EGFR activation, Rac2 translocation and NADPH oxidase activity. The results showed that UV irradiation induced EGFR phosphorylation and NADPH oxidase activity in a time dependent manner. Immunofluorescence microscopic study indicated that UV irradiation induced Rac2, a subunit of NADPH oxidase, translocation from cytoplasm to plasma membrane.
Conclusions: :
Taken together, our results suggest that UV–induced Dsg–2 degradation is due to ROS generation via EGFR activation and Rac2–mediated NADPH oxidase activation. Our study provides insights into understanding the molecular mechanisms leading to UV–induced cataract.
Keywords: cell adhesions/cell junctions • cataract • signal transduction