LEDGF binding to stress response element increases alphaB-crystallin expression in astrocytes with oxidative stress.
AlphaB-crystallin, known as a vertebrate lens protein, is a member of the small heat shock proteins (sHSP). AlphaB-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 alphaB-crystallin induction in activated astrocytes, which are enriched in the penumbra after transient focal cerebral ischemia. We also reported that alphaB-crystallin is significantly induced in astrocytes in the CA3 region of the hippocampus following KA-induced seizure. Here, we report that the expression of alphaB-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 alphaB-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 alphaB-crystallin induction was significantly suppressed by transfecting small interfering RNA (siRNA) targeting LEDGF. Together these results indicate that the H2O2-induced upregulations of alphaB-crystallin in astrocytes are mediated by the LEDGF-STRE interaction on alphaB-crystallin promoter.
Shin
Joo-Hyun
JH
Department of Anatomy and Center for Advanced Medical Education (BK21 project), Inha University School of Medicine, Inchon, Republic of Korea.
Piao
Chun-Shu
CS
Lim
Chae-Moon
CM
Lee
Ja-Kyeong
JK
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000502:physiology; D013997:Time Factors; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D038203:alpha-Crystallin B Chain; C119380:lens epithelium-derived growth factor; D006861:Hydrogen Peroxide