TY - JOUR
T1 - Regulatory differences in the stress response of hippocampal neurons and glial cells after heat shock
AU - Marcuccilli, Charles J.
AU - Mathur, Sameer K.
AU - Morimoto, Richard I.
AU - Miller, Richard J.
PY - 1996/1/15
Y1 - 1996/1/15
N2 - During periods of stress, cells depend on a transient, highly conserved, and regulated response to maintain homeostasis. This 'heat shock response' is mediated transcriptionally by a multigene family of heat shock factors (HSF). The presence of multiple HSF suggests that activation of a given HSF is stress-specific. Using Western blot analysis, we have demonstrated the inability of primary cultured rat hippocampal neurons to induce a heat shock response after hyperthermia. In contrast, secondary cultured rat glial cells demonstrated a robust response. Examination of whole-cell extracts from the two cell types with gel shift mobility analysis and Western blot analysis revealed that although glial cells express HSF1 and HSF2, hippocampal neurons only express HSF2. Incubation of whole-cell extracts with monoclonal antisera raised against HSF1 and HSF2 before gel shift mobility analysis demonstrated HSF1 DNA-binding activity in glial cells and HSF2 DNA-binding activity in neurons. HSF1 has been shown to be the principal mediator of heat-induced heat shock gene expression. These results suggest that the deficient heat shock response of hippocampal neurons at this developmental stage is attributable to a lack of HSF1 expression. Furthermore, these results suggest that considerations of selective neuronal vulnerability to environmental stress should include the principal mediators of the stress response, the HSF.
AB - During periods of stress, cells depend on a transient, highly conserved, and regulated response to maintain homeostasis. This 'heat shock response' is mediated transcriptionally by a multigene family of heat shock factors (HSF). The presence of multiple HSF suggests that activation of a given HSF is stress-specific. Using Western blot analysis, we have demonstrated the inability of primary cultured rat hippocampal neurons to induce a heat shock response after hyperthermia. In contrast, secondary cultured rat glial cells demonstrated a robust response. Examination of whole-cell extracts from the two cell types with gel shift mobility analysis and Western blot analysis revealed that although glial cells express HSF1 and HSF2, hippocampal neurons only express HSF2. Incubation of whole-cell extracts with monoclonal antisera raised against HSF1 and HSF2 before gel shift mobility analysis demonstrated HSF1 DNA-binding activity in glial cells and HSF2 DNA-binding activity in neurons. HSF1 has been shown to be the principal mediator of heat-induced heat shock gene expression. These results suggest that the deficient heat shock response of hippocampal neurons at this developmental stage is attributable to a lack of HSF1 expression. Furthermore, these results suggest that considerations of selective neuronal vulnerability to environmental stress should include the principal mediators of the stress response, the HSF.
KW - HSF
KW - HSP70
KW - glia
KW - heat shock
KW - hippocampus
KW - selective vulnerability
UR - http://www.scopus.com/inward/record.url?scp=0030048735&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030048735&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.16-02-00478.1996
DO - 10.1523/jneurosci.16-02-00478.1996
M3 - Article
C2 - 8551332
AN - SCOPUS:0030048735
SN - 0270-6474
VL - 16
SP - 478
EP - 485
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 2
ER -