Heat stress stimulates inositol trisphosphate release and phosphorylation of phosphoinositides in CHO and Balb C 3T3 cells.

Exposure of eukaryotic cells to elevated temperature leads to profound switches in cell metabolism and gene expression which may be involved in cellular homeostatic mechanisms. We have investigated the effect of heat shock (45 degrees C) on the metabolism of the phosphoinositides, a class of phospholipids involved in the function of Ca2+ -linked membrane receptors. Heat shock led to stimulation of phosphoinositide turnover in HA1-CHO and Balb C 3T3 cells, resulting in the rapid accumulation of inositol trisphosphate (IP3). Mitogenic and alpha 1 adrenergic stimulation, with serum or phenylephrine, led to similar increases in IP3. Heat shock also caused rapid increase in phosphorylation of polyphosphoinositides (PPI). Prolonged exposure to heat greater than 15 min at 45 degrees C led to progressive cellular toxicity which was associated with depletion of PPI. This decline in PPI concentration appeared to result from inhibition of PPI resynthesis. In this respect, heat may resemble some other types of cellular stresses in stimulating membrane phospholipases to deplete classes of membrane phospholipids. The induction of PPI turnover may, therefore, be involved in both pleiotropic responses to brief heat shock and toxicity resulting from prolonged thermal stress.