Osmotic regulation of the heat shock response in H4IIE rat hepatoma cells

The influence of cell hydration on the heat shock response was investigated in H4IIE hepatoma cells at the levels of HSP70 expression, MAP kinase acti vation, induction of c-jun and the RAP kinase phosphatase MKP-1, heat resis tance, and development of tolerance/sensitization to arsenite after a primi ng heat treatment. Induction of HSP70, MKP-1, and c-jun by heat was delayed , but more pronounced or sustained, under hyperosmotic conditions compared with normo- and hypo-osmotically exposed cells. Anisosmolarity per sc was i neffective to induce HSP70; some expression of the mRNAs for MKP-1 and c-ju n in response to hyperosmolarity nas found, but was small compared with the response to heat. Heat-induced activation of JNK-1 was increased under hyp erosmotic conditions and more sustained than the JNK-activity induced by hy perosmolarity at 37 degrees C, A prominent Erk-2 activation was found immed iately after heat shock under hypo- and normo-osmotic conditions, but Erk-2 activation was weak in hyperosmolarity-exposed cells. Despite anisosmotic alterations of the heat shock response at the molecular level, the heat res istance of H4IIE cells toward heat shock was not affected by ambient osmola rity, However, an osmolarity-dependent sensitization to arsenite was: induc ed by a priming heat shock. The osmodependence of the H4IIE cell response t o heat differs from that recently found in primary rat hepatocytes, The dat a are discussed in terms of cellular adaption mechanisms and their physiolo gical relevance.