title: Expression of Vascular Endothelial Growth Factor by Retinal Pigment Epithelial Cells Induced by Amyloid-β Is Depressed by an Endoplasmic Reticulum Stress Inhibitor.
abstract: OBJECTIVE
  Amyloid-β (Aβ) is a 36- to 43-amino-acid peptide that is a constituent of drusen, and it has been demonstrated to upregulate vascular endothelial growth factor (VEGF) expression by retinal pigment epithelial (RPE) cells. This study aimed to determine whether 4-phenylbutyl phosphonylacetate (PBA), a known endoplasmic reticulum (ER) stress inhibitor, can reduce Aβ-induced expression of VEGF in RPE cells.
  
  
  METHODS
  Aβ was added to the medium of regularly cultured or polarized ARPE-19 cells, a human RPE cell line, with or without PBA. The levels of VEGF and ER stress markers, namely GRP78/Bip, cleaved caspases 4 and 12 and GADD153/C-EBP homologous protein, were determined by enzyme-linked immunoassay, immunocytochemistry and Western blotting.
  
  
  RESULTS
  Exposure of ARPE-19 cells to Aβ induced GRP78/Bip expression and activated caspases 4 and 12; however, their expression was decreased by simultaneous exposure to PBA. Aβ increased the expression of VEGF both in regularly cultured and polarized ARPE-19 cells, but it was suppressed by PBA. PBA did not cause RPE cell apoptosis.
  
  
  CONCLUSIONS
  Aβ has been suggested to be involved in the development of age-related macular degeneration; therefore, our findings suggest that drugs that target ER stress should be considered for the treatment of age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Matsui
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Shu
authors.initials: S
authors.lastname: Kachi
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Ye
authors.forename: Shiang-Jyi
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Kei
authors.initials: K
authors.lastname: Takayama
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nagasaka
authors.forename: Tadasu
authors.initials: T
authors.lastname: Sugita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D015153:Blotting, Western; D002082:Butylamines / Q000494:pharmacology*; D053454:Caspase 12 / Q000378:metabolism; D053471:Caspases, Initiator / Q000378:metabolism; D002460:Cell Line; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C121358:4-phenylbutylamine; D016229:Amyloid beta-Peptides; D002082:Butylamines; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051742:Transcription Factor CHOP; C506444:CASP12 protein, human; C093516:CASP4 protein, human; D053454:Caspase 12; D053471:Caspases, Initiator