title: 17-AAG, a Hsp90 inhibitor, attenuates the hypoxia-induced expression of SDF-1alpha and ILK in mouse RPE cells.
abstract: The aim of this study was to investigate the changes of SDF-1alpha and ILK expression in mouse retinal pigment epithelium (RPE) cells in response to hypoxia, and the effect of 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a heat shock protein 90 (Hsp90) inhibitor, on the hypoxia-induced expression of SDF-1alpha and ILK. RPE cells were cultured with 200 micromol/L cobalt chloride (CoCl(2)) for different times (1, 3, 6, 12, 24, 72 h) to imitate chemical hypoxia. Pretreatment of 17-AAG was 1 h prior to hypoxic insult. Cellular viability after 17-AAG treatment was assessed by MTT assay, and the changes of SDF-1alpha and ILK expression were examined by RT-PCR and Western blot. Up-regulation of SDF-1alpha and ILK expression in response to hypoxia was observed. One hour pretreatment of 17-AAG could remarkably decreased the hypoxia-induced SDF-1alpha and ILK expression in vitro. Our results indicated that SDF-1alpha and ILK involved in the hypoxic response of RPE cells, and 1 h pretreatment of 17-AAG had an inhibitive effect on the hypoxia-induced SDF-1alpha and ILK expression.
authors.affiliation: Ophthalmology Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Ye Qing
authors.initials: YQ
authors.lastname: Wang
authors.forename: Xiao Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Xiao Dan
authors.initials: XD
authors.lastname: Wang
authors.forename: Bin Jie
authors.initials: BJ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099200:Scaffold Protein ILK
chemical_list: D016227:Benzoquinones; D054377:Chemokine CXCL12; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C112765:tanespimycin