Phenylarsine oxide inhibits heat shock protein 70 induction in cultured guinea pig gastric mucosal cells

Phenylarsine oxide (PAO) forms a stable ring complex with vicinal dithiols that can be reversed with 2,3- dimercaptopropanol (DMP) but not by dithioth reitol (DTT) or 2-mercaptoethanol (2-ME). PAO at 2 mu M or higher inhibited heat shock protein 70 (HSP70) induction within minutes in cultured guinea pig gastric mucosal cells exposed to heat (43 degrees C) for 30 min. PAO di d not affect the nuclear translocation and phosphorylation of heat shock fa ctor 1 (HSF1) induced by heat stress, but it completely blocked the binding activity of HSF1 to the heat shock element (HSE), leading to the block of expression of HSP70 mRNA and accumulation of HSP70 in the cells. These inhi bitions were completely reversed with 2 mM DMP but not with 0.1 mM DTT or 1 mM 2-ME, suggesting specific interactions between PAO and vicinal dithiol- containing molecules. Thioredoxin (Trx) reversed the inhibition of the bind ing activity of HSF1 in whole cell extracts prepared from PAO-treated, heat -stressed cells. Our results suggest that PAO may react with vicinal-contai ning molecules including Trx and specifically block the interaction between HSF1 and HSE.