17-AAG, a Hsp90 inhibitor, attenuates the hypoxia-induced expression of SDF-1alpha and ILK in mouse RPE cells

Mol Biol Rep. 2010 Mar;37(3):1203-9. doi: 10.1007/s11033-009-9490-x. Epub 2009 Mar 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoquinones / pharmacology*
  • Blotting, Western
  • Cell Hypoxia / drug effects
  • Cell Line
  • Chemokine CXCL12 / metabolism*
  • Gene Expression Regulation / drug effects*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • Lactams, Macrocyclic / pharmacology*
  • Mice
  • Protein Serine-Threonine Kinases / metabolism*
  • Retinal Pigment Epithelium / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Benzoquinones
  • Chemokine CXCL12
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • tanespimycin
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases