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Neural differentiation and the attenuated induction of HSP chaperones
Author(s) -
Oza Jay H,
Chen Wenjun,
Liu Alice Y.C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a962-b
Subject(s) - neural stem cell , microbiology and biotechnology , biology , heat shock protein , stem cell , progenitor cell , neural development , heat shock , neuroscience , neuron , hsp70 , cellular differentiation , gene , genetics
Selective neuronal vulnerability is a feature of various age‐related neural degenerative diseases such as Parkinson's, Huntington's, and ALS. Selective neuronal vulnerability also contributes to the limited ability of transplanted stem cells to replace diseased neural tissue. To better understand the molecular basis of neuronal vulnerability, we studied the regulation and function of the heat shock protein (HSP) chaperones in neural differentiation. Our results showed that differentiation of the NG108‐15 tumor neural progenitor cells from a stem cell like state to one that resembles a mature neuron is associated with an attenuated ability to mount the cytoprotective heat shock response. This attenuation was monitored by: activation of the HSF1 DNA‐binding activity, expression of the hsp70promoter‐luciferase reporter gene, and induction of the mRNA hsp70 and synthesis of the HSPs. This attenuated heat shock response appears to a common feature of the differentiated neuron. Further, we showed that conditioning heat shock and expression of HSP70 by gene transfer confer survival advantages to the differentiated neural cells as indexed by cell viability and caspase 3/7 activity. The possibility that the sustained activation of ERK1/2 in the differentiated neural cells may contribute to the attenuated heat shock response is being investigated. This research is supported in part by grants from the National Science Foundation (MCB‐0240009), and the NJ Commission on Spinal Cord Research (05‐3037‐SCR‐E‐0).