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 mRNA(hsp), 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.
Oza
Jay
J
Department of Cell Biology and Neuroscience, Division of Life Sciences, Rutgers State University of New Jersey, 604 Allison Road, Piscataway, NJ 08854-8082, USA.
Yang
Jingxian
J
Chen
Kuang Yu
KY
Liu
Alice Y-C
AY
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D017930:Genes, Reporter; D005910:Glioma / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D006358:Hot Temperature; D006822:Hybrid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D016501:Neurites / Q000648:ultrastructure; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C107835:Hspca protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D003994:Bucladesine