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• W3095432858 abstract "High glucose (HG)-induced oxidative stress contributes significantly to the pathogenesis of diabetic retinopathy. Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) has emerged as a key regulator of oxidative stress implicated in various pathological processes. However, whether PHLPP1 participates in the regulation of HG-induced oxidative stress injury of retinal ganglion cells (RGCs) in diabetic retinopathy is undetermined. The purpose of this study was to explore the potential role and molecular mechanism of PHLPP1 in regulating HG-induced injury of RGCs. Our data showed that PHLPP1 expression was markedly elevated in RGCs from diabetic rats and HG-exposed RGCs. Our functional assay elucidated that knockdown of PHLPP1 improved cell viability and decreased cell apoptosis and reactive oxygen species (ROS) production in HG-exposed RGCs. Additionally, upregulation of PHLPP1 lowered cell viability and increased cell apoptosis and ROS production in HG-exposed RGCs. Mechanistically, knockdown of PHLPP1 resulted in an increase in nuclear factor erythroid-2 related factor 2 (Nrf2) nuclear expression and Nrf2/antioxidant response element (ARE)-mediated transcription associated with upregulation of glycogen synthase kinase-3β (GSK-3β) phosphorylation. Moreover, inhibition of GSK-3β significantly reversed the suppressive effect of PHLPP1 overexpression on Nrf2/ARE activation. Notably, the protective effect of PHLPP1 knockdown on HG-induced injury in RGCs was markedly abolished by Nrf2 inhibition. In conclusion, Our findings demonstrate that downregulation of PHLPP1 activates Nrf2/ARE signaling to protect RGCs from HG-induced apoptosis and oxidative stress. This study indicates a potential role of PHLPP1 in regulating HG-induced injury of RGCs during the development and progression of diabetic retinopathy." @default.
• W3095432858 created "2020-11-09" @default.
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• W3095432858 date "2020-12-01" @default.
• W3095432858 modified "2023-10-16" @default.
• W3095432858 title "Downregulation of PHLPP1 ameliorates high glucose-evoked injury in retinal ganglion cells by attenuating apoptosis and oxidative stress through enhancement of Nrf2 activation" @default.
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• W3095432858 doi "https://doi.org/10.1016/j.yexcr.2020.112344" @default.
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