REDUCED INDUCTION OF HSP70 IN PC12 CELLS DURING NEURONAL DIFFERENTIATION

Rat pheochromocytoma PC12 cells differentiate into nonreplicating neur onal cells with neurite extensions in response to nerve growth factor (NGF), To gain better understanding of the regulation of stress respon ses in neuronal cells, we examined the induction of HSP70, HSP70 mRNA, and heat shock factor 1 (HSF1) DNA-binding activity following treatme nt by heat shock or with sodium arsenite or amino acid analogue in PC1 2 cells treated with or without NGF, The induction of HSP70 and HSP70 mRNA following these stresses was diminished in the differentiated PC1 2 cells compared to the undifferentiated cells, whereas the HSF1 DNA-b inding activity was enhanced in the differentiated PC12 cells, This ph enomenon was characteristic of the differentiated neuronal cells rathe r than growth-arrested cells. Thus, neuronal cells appear to show an a ltered stress response depending on their differentiation state, and t he diminished HSP70 expression in the differentiated neuronal cells ma y explain the sensitivity of neuronal cells to pathophysiological stre ssors.