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• W2313722511 abstract "Abstract To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 °C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45 α (GADD45 α ) expression was markedly upregulated. Transient knockdown of GADD45 α partially attenuated light-damage-induced apoptosis in ARPE-19 cells, whereas GADD45 α overexpression dramatically increased it. These results demonstrate the critical function of GADD45 α in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45 α was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45 α gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45 α expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45 α expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment." @default.
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• W2313722511 date "2016-02-29" @default.
• W2313722511 modified "2023-10-16" @default.
• W2313722511 title "Upregulation of GADD45α in light-damaged retinal pigment epithelial cells" @default.
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• W2313722511 doi "https://doi.org/10.1038/cddiscovery.2016.13" @default.
• W2313722511 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4979445" @default.
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