Heat shock factor 2 is involved in the upregulation of alphaB-crystallin by high extracellular potassium.
alphaB-Crystallin, a member of the small heat shock protein (HSP) family, accumulates in reactive astrocytes in a variety of pathological conditions. We previously reported the upregulation of alphaB-crystallin in response to high extracellular potassium concentration. In the present study, we investigated the regulatory mechanism of alphaB-crystallin expression by KCl. When human glioma U-251MG cells were exposed to continuous KCl treatment, induction of alphaB-crystallin mRNA was observed after 8 h and persisted for a few days. Functional promoter analysis using deletion and mutation constructs revealed that the proximal heat shock element (HSE-P), which contributes to heat shock induction in HeLa cells, is essential for transcriptional activation of the alphaB-crystallin gene by KCl in U-251MG cells. Gel mobility shift and antibody supershift assays showed that KCl induces the HSE-binding activity of heat shock factor (HSF) 2, while heat shock induces that of HSF1. This is the first demonstration that HSF2 can be activated by KCl and is involved in the upregulation of alphaB-crystallin gene expression in glial cells.
Sadamitsu
C
C
Division of Disease Genes, Institute of Genetic Information, Kyushu University, Fukuoka 812-8582, Japan. aiwaki@gen.kyushu-u.ac.jp
Nagano
T
T
Fukumaki
Y
Y
Iwaki
A
A
D001665:Binding Sites / Q000187:drug effects; D003459:Crystallins / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005910:Glioma / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018882:Heat Stress Disorders / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011189:Potassium Chloride / Q000378:metabolism / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000819:agonists / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D003459:Crystallins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C070389:HSF2 protein, human; D011189:Potassium Chloride