The protein kinase inhibitor, H-7, suppresses heat induced activation of heat shock transcription factor 1

Mol Cell Biochem. 1999 Jul;197(1-2):129-35. doi: 10.1023/a:1006937513154.


We investigated the effects of a protein kinase (PK) inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride), on the regulation of heat shock protein (hsp)72 gene expression in a human glioblastoma cell line (A-172) using a gel mobility-shift assay and Western blot analysis. Heat shock transcription factor 1 (HSF1) was phosphorylated immediately after heat treatment (44 degrees C, 30 min) and the phosphorylation of HSF1 was suppressed by H-7. The increase in DNA binding ability of HSFI to heat shock element (HSE) by heat shock was significantly suppressed by the addition of H-7 in a dose-dependent manner. Similarly, the accumulation of hsp72 by heat shock was suppressed by the addition of H-7 in a dose-dependent manner. Since H-7 is known to be a potent inhibitor of some PKs, especially calcium-dependent PK (PKC), cyclicAMP-dependent PK (PKA) and cyclicGMP-dependent PK (PKG), it is possible that the activation of HSF1 by phosphorylation and subsequent hsp72 gene expression are dependent on some of those PKs. The nature of H-7 as a non-specific inhibitor for PKs is discussed in relation to its availability for regulation of heat sensitivity of cells depending on cellular level of hsp72.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology*
  • Base Sequence
  • DNA Primers
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology*
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins / antagonists & inhibitors
  • Heat-Shock Proteins / metabolism
  • Hot Temperature
  • Humans
  • Kinetics
  • Protein Kinase Inhibitors*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured


  • DNA Primers
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Heat-Shock Proteins
  • Protein Kinase Inhibitors
  • Transcription Factors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine