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

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Abstract

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°C, 30 min) and the phosphorylation of HSF1 was suppressed by H-7. The increase in DNA binding ability of HSF1 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.

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Authors and Affiliations

  1. Department of Biology, Nara Medical University, Kashihara, Nara, Japan

    Ken Ohnishi, Xinjiang Wang, Akihisa Takahashi, Hideki Matsumoto & Takeo Ohnishi

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  1. Ken Ohnishi
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  2. Xinjiang Wang
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  3. Akihisa Takahashi
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  4. Hideki Matsumoto
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  5. Takeo Ohnishi
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Ohnishi, K., Wang, X., Takahashi, A. et al. The protein kinase inhibitor, H-7, suppresses heat-induced activation of heat shock transcription factor 1. Mol Cell Biochem 197, 129–135 (1999). https://doi.org/10.1023/A:1006937513154

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