Abstract
Background Casein kinase 2-interacting protein-1 (CKIP-1) has been proved to be associated with complications of diabetes. Diabetic retinopathy is a main diabetic complication which usually leads to blindness. The current study aims to investigate the role of CKIP-1 in high glucose-treated retinal pigment epithelial (RPE) cells which is a component of blood-retinal barriers. Methods The RPE cells, ARPE-19, are treated with high glucose to mimic the diabetic stimulation. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively. Results CKIP-1 was expressed at a lower level in high glucose-treated cells than in normal glucose cells. Overexpression of CKIP-1 enhanced the Nrf2 translocation to the nucleus. Furthermore, high glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. Also, CKIP-1 regulates the p62/Keap1/Nrf2 signaling, which might be the potential mechanism in this model. Conclusion In conclusion, CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose.
Highlights
Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes leading to vision impairment and even blindness [1]
To study the role of Casein kinase 2-interacting protein-1 (CKIP-1) in HG-induced ARPE-19 cells, CKIP-1 was overexpressed in ARPE-19 cells by transfection with pcDNA3.1-CKIP-1 using Lipofectamine 3000 (Invitrogen) for 48 h. e ORF sequence of human CKIP-1 (GenBank No NM_016274) cDNA was amplified by RT-PCR and subsequently cloned into vector pcDNA3.1 (Invitrogen, USA). e pcDNA3.1-empty vector plasmids were transfected as negative control
High glucose treatment triggered the reduction of CKIP-1 levels and the activation of oxidative stress and autophagy in retinal pigment epithelial cells
Summary
Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes leading to vision impairment and even blindness [1]. Research has reported that continuing stimulation of hyperglycemia on RPE cells induces oxidative stress and cell apoptosis [7,8,9], which promotes BRB injury and subsequent DR progression. Upregulation of CKIP-1 suppressed apoptosis and oxidative stress by inhibiting Keap and activating Nrf2/ARE signaling in hippocampal neurons [10]. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively. High glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose
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