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Ocular endoplasmic reticulum stress and inflammation is attenuated by supplementation with muscadine grape polyphenols in vitro and in vivo (1045.2)
Author(s) -
Ha JungHeun,
Gu Liwei,
Li Qiuhong,
Chung Soonkyu
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1045.2
Subject(s) - unfolded protein response , proinflammatory cytokine , inflammation , endoplasmic reticulum , apoptosis , retinal , cytokine , microbiology and biotechnology , chemistry , medicine , cancer research , immunology , endocrinology , biology , biochemistry
Chronic ER stress and inflammation in retinal epithelium are critical risk factors for the pathogenesis of vision‐threatening diseases such as diabetic retinopathy. The aim of this study is to investigate the protective effects of muscadine grape polyphenols (MGP) against ocular ER stress and inflammation. In human retinal cells (ARPE‐19), 50‐100 μg/mL of MGP treatment significantly reduced thapsigragin‐mediated 1) vascular endothelial growth factor (VEGF) secretion, 2) ER stress‐markers of p‐eIF2α, ATF4, p‐JNK, p‐p38 and CHOP, and unfolded protein responses, and 3) early apoptotic cell death (~40 %). It was primarily due to a decrease of intracellular calcium release (p<0.001) and subsequent signal transduction downstream by MGP. In addition, MGP treatment was also effective in attenuating TNFα‐induced proinflammatory gene expressions, such as IL‐1β, IL‐6 and MCP‐1, (p<0.001) in ARPE‐19 cells by inhibiting MAP Kinase‐NFκB axis activation. Moreover, supplementation with MGP for 1 week in C57BL/6 mice led to 1) a remarkable decrease of LPS‐inducible proinflammatory cytokine expression and leukocyte infiltration into eyes, and 2) protection of retinal epithelial leakage against inflammation. Our study suggests that MGP may provide a novel dietary strategy to prevent vision‐threatening retinal diseases.