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Mutual enhancement between high‐mobility group box‐1 and NADPH oxidase‐derived reactive oxygen species mediates diabetes‐induced upregulation of retinal apoptotic markers
Author(s) -
Ghulam M.,
Abu El Asrar A.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0062
Subject(s) - nadph oxidase , apocynin , downregulation and upregulation , reactive oxygen species , oxidative stress , retina , diabetes mellitus , retinal , diabetic retinopathy , hmgb1 , chemistry , nox4 , endocrinology , medicine , apoptosis , biology , biochemistry , inflammation , neuroscience , gene
Summary We hypothesized that a novel mechanism exists where HMGB 1and NADPH oxidase ( NOX )‐derived ROS are mutually enhanced in the diabetic retina, which may be a novel mechanism for promoting upregulation of retinal apoptotic markers induced by diabetes. To test this hypothesis we analyzed the vitreous samples from PDR and nondiabetic patients, retinas from rats and human retinal microvascular endothelial cells. We found that HMGB 1 and the oxidative stress marker protein carbonyl content levels in the vitreous fluid from PDR patients were significantly higher than in controls. There was a significant positive correlation between vitreous fluid levels of HMGB 1 and the levels of protein carbonyl content. HMGB 1 enhanced interleukin‐1 β , ROS , NOX 2, and PARP ‐1 and cleaved caspase‐3 expression by HRMEC . Diabetes and intravitreal injection of HMGB 1 in normal rats induced significant upregulation of ROS , NOX 2, PARP ‐1 and cleaved caspase‐3 in the retina. Constant glycyrrhizin and apocynin intake from onset of diabetes did not affect the metabolic status of the diabetic rats, but restored these increased mediators to control values. Our results suggest that there is a mutual enhancement between HMGB 1 and NOX ‐derived ROS in the diabetic retina.