Abstract
Purpose: To investigate the significance of calcium-independent phospholipase A2, group VIA (iPLA2-VIA), in RPE cell survival following responses to sodium iodate (SI) in cell cultures. Methods: The human retinal pigment epithelium (RPE) cell line (ARPE-19) cells and primary mouse-RPE cultures were treated with SI to induce cell death. Cells were transfected with an iPLA2-VIA promoter-luciferase construct to evaluate the regulation of iPLA2-VIA after exposure to SI. PCR analysis, western blot analysis, and activity assays were performed to evaluate the mRNA level, protein level, and activity levels of iPLA2-VIA after SI exposure. Inhibitors of iPLA2-VIA were used to explore a potential protective role in cells exposed to SI. Primary RPE cell cultures were grown from iPLA2-VIA knockout mice and wild-type mice. The cultures were exposed to SI to investigate a possible increased protection against SI in iPLA2-VIA knockout mice compared to wild-type mice. Results: The study revealed upregulation of iPLA2-VIA expession (promoter activity, iPLA2-VIA mRNA, iPLA2-VIA protein, and iPLA2-VIA protein activity) in ARPE-19 cells exposed to SI. SI-induced cell death was shown to be inhibited by iPLA2-VIA-specific inhibitors in ARPE-19 cell cultures. RPE cultures from iPLA2-VIA knockout mice were less vulnerable to SI-induced cell death compared to RPE cultures from wild-type mice. Conclusions: SI -induced RPE cell death involves iPLA2-VIA upregulation and activation, and amelioration of SI-induced RPE cell death can be facilitated by inhibitors of iPLA2-VIA. Thus, we suggest iPLA2-VIA as a possible pharmaceutical target to treat RPE-related retinal diseases.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular Vision |
| Vol/bind | 20 |
| Sider (fra-til) | 511-21 |
| Antal sider | 11 |
| ISSN | 1090-0535 |
| Status | Udgivet - 25 apr. 2014 |
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