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Mi Hye Song, Beth Elledge, Weilue He, Srinivas Sripathi, Kelly Hanes, Sarah Mets, Eric Vertin, Parrisha Louis, Wan Jin Jahng; Light-Induced Stress Leads to Cytoskeletal Reorganization in the Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3347.
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We aim to understand how cytoskeletal proteins in the retina respond to oxidative stress and how these responses affect apoptotic signaling of retina cells. We determined the role of vimentin, an intermediate filament, in the retina under stress conditions. Previously, proteomic analysis of the retina revealed that the expression levels of vimentin and protein phosphatase 2A (PP2A) are significantly increased when mice are exposed under continuous light for 7 days compared to a condition of 12h light/dark cycling exposure. When melatonin is administered to animals while they are exposed to continuous light, the levels of vimentin and PP2A return to a normal level. Further, vimentin has been shown to be a target of PP2A that directly binds vimentin and dephosphorylates it. Vimentin is present in all mesenchymal cells, and often used as a differentiation marker. Like other intermediate filaments, vimentin acts to maintain cellular integrity; however, vimentin may play a role in adhesion, migration, cellular survival and signaling in the retina.
In vivo, female mice (12 weeks of age) were housed under a 12h light/12h dark cycling condition (250-300 lux) for 2 weeks. Animals were divided into three groups (12 mice/group). The first group of mice (light/dark group) were housed in the 12 h light/ 12 h dark condition and treated with melatonin vehicle solution (0.3% ethanol-saline); the second group (constant light group) were housed in constant room light for 7 days and also treated with vehicle solution; the third group (melatonin treated group) were kept in constant room light for 7 days and treated with melatonin via intraperitoneal injection at a dose of 50ug/mouse. In vitro, rat retinal cells and ARPE19 cells were exposed to light (700-5000 lux). We used biochemistry and cell biology to examine what roles vimentin might play in the retina.
Upregulation of PP2A positively correlates with the levels of vimentin upon light-induced stress. Stabilization of vimentin appears to be achieved by inhibition of protein kinase such as S6 Kinase or enhancing the activity of protein phosphatase 2A.
Our results suggest that external stress enhances PP2A activity, thereby stabilizing vimentin by directly dephosphorylating it, and preventing vimentin from caspase-dependent protein degradation and the activation of apoptosis. Phosphorylation may result in depolymerized vimentin, leading to nonfilamentous particles. We hypothesize that a stabilized vimentin might act as an antiapoptotic agent when cells are under stress.
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