title: Endoplasmic reticulum stress induces retinal endothelial permeability of extracellular-superoxide dismutase.
abstract: The aim of this study was to determine the reasons why the intravitreal level of extracellular-superoxide dismutase (EC-SOD) increases in proliferative diabetic retinopathy patients by the investigation of two possibilities: first, change of EC-SOD expression in the retina; and secondly, leakage of EC-SOD through the endothelial monolayer by the treatment with endoplasmic reticulum (ER) stress inducers because ER stress is known to be involved in the vascular impairment in diabetic retinopathy. Intravitreous injection of tunicamycin in mice increased the permeability of tracer dye across retinal blood vessels while the retinal EC-SOD mRNA level was not changed. The leakage of EC-SOD through the retinal endothelial cell layer was elevated by the treatment with thapsigargin or tunicamycin. The expression of claudin-5 was significantly decreased by the treatment with the ER stress inducers. These phenomena were significantly suppressed by the pre-treatment of endothelial cells with a chemical chaperone 4-phenylbutyric acid. Our observations suggest that ER stress leads to the down-regulation of claudin-5 among tight junction proteins and may induce the elevation of endothelial permeability and leakage of EC-SOD into the vitreous body.
authors: Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Daigaku-nishi, Gifu, Japan. adachi@gifu-pu.ac.jp
authors: Tetsuo
authors: T
authors: Adachi
authors: Hiroyuki
authors: H
authors: Yasuda
authors: Shinsuke
authors: S
authors: Nakamura
authors: Tetsuro
authors: T
authors: Kamiya
authors: Hirokazu
authors: H
authors: Hara
authors: Hideaki
authors: H
authors: Hara
authors: Tsunehiko
authors: T
authors: Ikeda
mesh_terms: D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D062507:Claudin-5; D057167:Claudins / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000201:enzymology; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004727:Endothelium / Q000201:enzymology; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D051381:Rats; D012160:Retina / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D014822:Vitreous Body / Q000201:enzymology*
chemical_list: D062507:Claudin-5; D057167:Claudins; C491511:Cldn5 protein, mouse; D014415:Tunicamycin; D019284:Thapsigargin; C499090:Sod3 protein, mouse; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase