LEDGF binding to stress response element increases αB-crystallin expression in astrocytes with oxidative stress

Joo Hyun Shin, Chun Shu Piao, Chae Moon Lim, Ja Kyeong Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

αB-crystallin, known as a vertebrate lens protein, is a member of the small heat shock proteins (sHSP). αB-crystallin is abundantly expressed in the vertebrate lens and striated muscles and it is also expressed constitutively in other tissues including the central nervous system (CNS). In our previous report, we showed αB-crystallin induction in activated astrocytes, which are enriched in the penumbra after transient focal cerebral ischemia. We also reported that αB-crystallin is significantly induced in astrocytes in the CA3 region of the hippocampus following KA-induced seizure. Here, we report that the expression of αB-crystallin is upregulated in H2O2-treated primary astrocyte cultures, which was prepared from newborn male Sprague-Dawley rats and that the proximal 408 bp of the αB-crystallin promoter harboring stress response element (STRE) is responsible for this induction. This effect of H2O2 was found to be virtually abolished by introducing mutations into STRE, and these mutations also impaired increased lens epithelial derived growth factor (LEDGF) binding to STRE after H2O2 treatment. Moreover, LEDGF was induced in primary astrocyte cultures after H2O2 treatment and αB-crystallin induction was significantly suppressed by transfecting small interfering RNA (siRNA) targeting LEDGF. Together these results indicate that the H2O2-induced upregulations of αB-crystallin in astrocytes are mediated by the LEDGF-STRE interaction on αB-crystallin promoter.

Original languageEnglish (US)
Pages (from-to)131-136
Number of pages6
JournalNeuroscience Letters
Volume435
Issue number2
DOIs
StatePublished - Apr 18 2008

Keywords

  • Astrocyte
  • HO
  • LEDGF
  • STRE
  • αB-crystallin

ASJC Scopus subject areas

  • Neuroscience(all)

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