Arsenite pre-conditioning reduces UVB-induced apoptosis in corneal epithelial cells through the anti-apoptotic activity of 27 kDa heat shock protein (HSP27).
Exposure to ultraviolet (UV) light poses a health risk for eye disease, and solar ultraviolet in the B range (UVB, 280-320 nm) is known to be related to various corneal disorders. In this study, we investigated whether pre-conditioning of cells with arsenite (AsO2(-1)) can reduce UVB-induced apoptosis in human corneal epithelial cells, and whether the anti-apoptotic activity of 27 kDa heat shock protein (HSP27), a small heat shock protein, plays a role in this protection. UVB at levels comparable to physiologic solar exposure induces apoptosis of corneal epithelial cells in culture, demonstrated by activation of caspase 9 and caspase 3, and DNA fragmentation. When cells were pre-conditioned with arsenite prior to UVB exposure, the UVB-induced cell death was reduced, and UVB-induced activation of caspases and DNA fragmentation was inhibited. When cells were pre-treated with SB 203580, which inhibits HSP27 phosphorylation through inhibition of p38 MAP kinase activation, the arsenite-induced reduction of UVB-induced apoptosis was partially reversed. Arsenite pre-conditioning inhibited UVB-induced apoptosis in a two-phase pattern, which was temporally correlated with arsenite-induced HSP27 expression and phosphorylation. Neutralization of intracellular HSP27 with its antibody reduced arsenite's inhibition of UVB-induced caspase3 activation. Our results suggest that forms of stress that upregulate HSP27 and its phosphorylation may be useful as novel approaches to prevent adverse ocular effects arising from UV exposure in humans.
Shi
Biao
B
Department of Dermatology, University of California Davis School of Medicine, Davis, California 95616, USA.
Isseroff
R Rivkah
RR
D017209:Apoptosis; D018053:Arsenites / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018053:Arsenites; D006360:Heat-Shock Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C015001:arsenite