NDLI: Intermittent high glucose-induced oxidative stress modulates retinal pigmented epithelial cell autophagy and promotes cell survival via increased HMGB1

Content Provider	Springer Nature : BioMed Central
Author	Zhang, Wei Song, Jian Zhang, Yue Ma, Yingxue Yang, Jing He, Guanghui Chen, Song
Abstract	Background In this study, we evaluated the effects of intermittent high glucose on oxidative stress production in retinal pigmented epithelial (RPE) cells and explored whether the mechanisms of autophagy and apoptosis in oxidative stress are associated with high-mobility group box 1 (HMGB1) protein. Methods Cultured human RPE cell line ARPE-19 cells were exposed to intermittent high glucose-induced oxidative stress. Reactive oxygen species (ROS) was determined by 2′, 7′-dichlorofluorescin diacetate (DCFH-DA); and malonyldialdehyde (MDA), superoxide dismutase (SOD) by commercial kits. Transmission electron microscopy was used to observe the generation of autophagosome. And MTT assay was used to examine the effect of autophagy on cell viability. For the inhibition experiments, cells were pre-incubated with lysosomal inhibitors NH4Cl or N-acetyl cysteine (NAC).Western blot was used to measure the expression patterns of autophagic markers, including LC3 and p62. The expression of HMGB1 was detected by immunohistochemistry.Cells were pre-incubated with HMGB1 inhibitor ethyl pyruvate (EP) ,then detected the expression pattern of autophagic markers and level of cellular ROS. Results We found that intermittent high glucose significantly increased oxidative stress levels (as indicated by ROS, MDA, SOD), increased in the generation of autophagosome, decreased the level of p62, induced conversion of LC3 I to LC3 II. We further demonstrated that the NH4Cl/NAC inhibited intermittent high glucose-induced autophage by altered level of LC3 and p62. Intermittent high glucose-induced autophagy is independent of HMGB1 signaling, inhibition of HMGB1 release by EP decreased expression pattern of autophagic markers and level of cellular viability. Conclusions Under intermittent high glucose condition, autophagy may be required for preventing oxidative stress-induced injury in RPE. HMGB1 plays important roles in signaling for both autophagy and oxidative stress.
Related Links	https://bmcophthalmol.biomedcentral.com/counter/pdf/10.1186/s12886-018-0864-5.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	14712415
DOI	10.1186/s12886-018-0864-5
Journal	BMC Ophthalmology
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2018-08-06
Access Restriction	Open
Subject Keyword	Ophthalmology Intermittent high glucose HMGB1 Oxidative stress Autophagy Retinal pigment epithelium cell
Content Type	Text
Resource Type	Article
Subject	Ophthalmology
Journal Impact Factor	1.7/2023
5-Year Journal Impact Factor	2/2023

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