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

alpha B-crystallin, known as a vertebrate lens protein, is a member of the small heat shock proteins (sHSP). alpha B-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 alpha B-crystallin induction in activated astrocytes, which are enriched in the penumbra after transient focal cerebral ischemia. We also reported that alpha B-crystallin is significantly induced in astrocytes in the CA3 region of the hippocarnpus following KA-induced seizure. Here, we report that the expression of alpha B-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 alpha B-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 alpha B-crystallin induction was significantly suppressed by transfecting small interfering RNA (siRNA) targeting LEDGE Together these results indicate that the H2O2-induced upregulations of alpha B-crystallin in astrocytes are mediated by the LEDGF-STRE interaction on alpha B-crystallin promoter. (c) 2008 Elsevier Ireland Ltd. All rights reserved.