Protein kinase Cµ plays an essential role in hypertonicity-induced heat shock protein 70 expression

Heat shock protein 70 (HSP70), which evidences important functions as a molecular chaperone and anti-apoptotic molecule, is substantially induced in cells exposed to a variety of stresses, including hypertonic stress, heavy metals, heat shock, and oxidative stress, and prevents cellular damage under...

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Bibliographic Details
Published in:Experimental & molecular medicine 2008, Vol.40 (6), p.596-606
Main Authors: Lim, Yun-Sook, Lee, Jae-Seon, Huang, Tai-Qin, Seo, Jeong-Sun
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Medical Biochemistry
Molecular Medicine
Original
Stem Cells
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Summary:Heat shock protein 70 (HSP70), which evidences important functions as a molecular chaperone and anti-apoptotic molecule, is substantially induced in cells exposed to a variety of stresses, including hypertonic stress, heavy metals, heat shock, and oxidative stress, and prevents cellular damage under these conditions. However, the molecular mechanism underlying the induction of HSP70 in response to hypertonicity has been characterized to a far lesser extent. In this study, we have investigated the cellular signaling pathway of HSP70 induction under hypertonic conditions. Initially, we applied a variety of kinase inhibitors to NIH3T3 cells that had been exposed to hypertonicity. The induction of HSP70 was suppressed specifically by treatment with protein kinase C (PKC) inhibitors (Gö6976 and GF109203X). As hypertonicity dramatically increased the phosphorylation of PKCµ, we then evaluated the role of PKCµ in hypertonicity-induced HSP70 expression and cell viability. The depletion of PKCµ with siRNA or the inhibition of PKCµ activity with inhibitors resulted in a reduction in HSP70 induction and cell viability. Tonicity-responsive enhancer binding protein (TonEBP), a transcription factor for hypertonicity-induced HSP70 expression, was translocated rapidly into the nucleus and was modified gradually in the nucleus under hypertonic conditions. When we administered treatment with PKC inhibitors, the mobility shift of TonEBP was affected in the nucleus. However, PKCµ evidenced no subcellular co-localization with TonEBP during hypertonic exposure. From our results, we have concluded that PKCµ performs a critical function in hypertonicity-induced HSP70 induction, and finally cellular protection, via the indirect regulation of TonEBP modification.
ISSN:1226-3613
2092-6413
DOI:10.3858/emm.2008.40.6.596