Reduced Induction of HSP70 in PC12 Cells during Neuronal Differentiation

Abstract

Rat pheochromocytoma PC12 cells differentiate into nonreplicating neuronal cells with neurite extensions in response to nerve growth factor (NGF). To gain better understanding of the regulation of stress responses in neuronal cells, we examined the induction of HSP70, HSP70 mRNA, and heat shock factor 1 (HSF1) DNA-binding activity following treatment by heat shock or with sodium arsenite or amino acid analogue in PC12 cells treated with or without NGF. The induction of HSP70 and HSP70 mRNA following these stresses was diminished in the differentiated PC12 cells compared to the undifferentiated cells, whereas the HSF1 DNA-binding activity was enhanced in the differentiated PC12 cells. This phenomenon was characteristic of the differentiated neuronal cells rather than growth-arrested cells. Thus, neuronal cells appear to show an altered stress response depending on their differentiation state, and the diminished HSP70 expression in the differentiated neuronal cells may explain the sensitivity of neuronal cells to pathophysiological stressors.