title: Regulation of extracellular-superoxide dismutase in rat retina pericytes.
abstract: Diabetic retinopathy (DR) is regarded as a disease of the retinal microvascular system and metabolic abnormalities that are characteristic of oxidative stress and endoplasmic reticulum (ER) stress have been identified in the retina. Pericytes are known to be susceptible to oxidative stress and selective dropout of pericytes is one of the earliest pathological changes in DR. Extracellular-superoxide dismutase (EC-SOD) is a major antioxidative enzyme and protects vascular cells from the damaging effects of superoxide. Treatment with own conditioned medium significantly decreased EC-SOD expression in pericytes, while the expression of vascular endothelial growth factor and tumor necrosis factor-α were elevated. The addition of chemical chaperone 4-phenyl butyric acid significantly suppressed the effects of conditioned medium on EC-SOD and GRP78, a prominent ER-resident chaperone. Moreover, the cell viability of pericytes changed in a manner similar to that of EC-SOD expression. These results suggest that the expressions of EC-SOD should be regulated, at least partially, through ER stress. Continuous flow of culture media neutralized the ER-stress triggered decrease of EC-SOD expression. The stagnation of factors related to ER-stress around pericytes might reduce EC-SOD expression under pathophysiological conditions such as retinal edema, and this could induce and/or promote the intraretinal microvascular impairment and development of pathogenesis in DR.
authors.affiliation: Department of Biomedical Pharmaceutics, Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. adachi@gifu-pu.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasuda
authors.forename: Kazunari
authors.initials: K
authors.lastname: Aida
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kamiya
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hosoya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terasaki
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D018384:Oxidative Stress / Q000187:drug effects; D020286:Pericytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D016133:Polymerase Chain Reaction; D051381:Rats; D012160:Retina / Q000166:cytology*; D013482:Superoxide Dismutase / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013482:Superoxide Dismutase