Osmotic regulation of the heat shock response in primary rat hepatocytes

Open Access
Publisher Website
Google Scholar
Abstract
The influence of cell hydration and taurine on the heat shock response was studied in primary rat hepatocytes. Heat-induced accumulation of inducible heat shock protein 70 (HSP70) mRNA and protein was increased under hypo-osmotic conditions. In contrast, hyper-osmotic exposure blocked the HSP70 response during an 8-hour recovery, and this was paralleled by a reduction of overall protein synthesis and an impairment of thermotolerance. Taurine counteracted the hyper-osmotic inhibition of heat-induced HSP70 expression, but increased overall protein synthesis only slightly. A rapid and transient activation of the stress-activated protein kinase, JNK-2, was triggered by hyper-osmolarity, whereas the JNK-2 response to hypo-osmolarity was delayed. JNK-2 activation in response to heat was suppressed by hypo-osmolarity, but was markedly increased under hyper-osmotic conditions. The latter effect was blocked by taurine. A pronounced induction of the mRNA for the MAP-kinase phosphatase, MKP-1, in response to heat was observed during hypo- and normo-osmolarity, but no MKP-1 induction was found under hyper-osmotic conditions, although hyper-osmolarity itself led to accumulation of small levels of MKP-1 mRNA. Also, the block of heat-induced MKP-1 mRNA expression by hyper-osmolarity was abolished in the presence of taurine. The data provide evidence for a role of cellular hydration and taurine in the protection of liver parenchymal cells against heat injury via regulation of HSP70 expression and the balance between JNK-2 and MKP-1 activity.
Funding Information
  • Deutsche Forschungsgemeinschaft, the Leibniz Prize and the Fonds der Chemischen Industrie, Frankfurt, Germany