Changes in the regulation of heat shock gene expression in neuronal cell differentiation
Neuronal differentiation of the NG108-15 neuroblastoma–glioma hybrid cells is accompanied by a marked attenuation in the heat shock induction of the Hsp70-firefly luciferase reporter gene activity. Analysis of the amount and activation of heat shock factor 1, induction of mRNAhsp, and the synthesis and accumulation of heat shock proteins (HSPs) in the undifferentiated and differentiated cells suggest a transcriptional mechanism for this attenuation. Concomitant with a decreased induction of the 72-kDa Hsp70 protein in the differentiated cells, there is an increased abundance of the constitutive 73-kDa Hsc70, a protein known to function in vesicle trafficking. Assessment of sensitivity of the undifferentiated and differentiated cells against stress-induced cell death reveals a significantly greater vulnerability of the differentiated cells toward the cytotoxic effects of arsenite and glutamate/glycine. This study shows that changes in regulation of the HSP and HSC proteins are components of the neuronal cell differentiation program and that the attenuated induction of HSPs likely contributes to neuronal vulnerability whereas the increased expression of Hsc70 likely has a role in neural-specific functions.
KeywordsHeat shock gene expression Neuronal cell differentiation Heat shock protein
We are grateful to Dr. Mark Plummer of the Department of Cell Biology and Neuroscience for providing us with the rat embryonic hippocampal neuron culture (Magby et al. 2006). We thank Dr. Gutian Xiao for the Hsp70 knockout MEF. This work was supported in part by grants from the NSF (MCB0240009) and NJ Commission on Spinal Cord Research (05-3037-SCR-E-0).
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