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Boris Busov, Mercy D Pawar, Cagri G Besirli; The role of PI 3-kinase signaling in photoreceptor cell survival. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2398.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze the effects of the Phosphatidylinositol 3-Kinase-Akt (PI3K) signaling in the apoptosis pathway in photoreceptor cells
661 W photoreceptor cells were treated with PI3K inhibitor and cell survival was analyzed. Activities of caspases were measured. Expression of proteins involved in PI3K-Akt signaling were analyzed with Western blotting. Expression and phosphorylation of Akt were determined by immunohistochemistry in the mouse retina after experimental retinal detachment. The effect of PI3K signaling on the expression of photoreceptor neuroprotective protein Faim2 was evaluated. Faim2 knockout mice were used to determine the interaction between Faim2 and PI3K signaling in the photoreceptors.
PI3K inhibition led to reduced Akt phosphorylation in the 661 w cells. Total Akt levels remained stable in cells treated the PI3K inhibitor. Treatment of cells with various concentrations of PI3K inhibitor demonstrated increased cell death in a dose-dependent manner. Expression of PI3K target Akt was seen throughout the retina in mice. Retinal detachment led to increased phosphorylation of Akt in the photoreceptors specifically. Even though the total Akt levels were similar between wild type and Faim2 knockout mice at baseline, there was minimal Akt phosphorylation in Faim2 knockout mice at baseline compared with wild type controls. Retinal detachment led to Akt phosphorylation only in the wild type mouse photoreceptors and no change was seen in Faim2 knockout retina.
PI3K signaling is important in the survival of photoreceptor cells in vitro. In vivo data from Faim2 knockout animals indicate that downstream PI3K signaling may be dependent on the presence of functional Faim2 protein in the cells.
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