Comparison of the heat shock response in cultured cortical neurons and astrocytes

Nishimura, Robert N.; Dwyer, Barney E.; Clegg, Kerry B.; Cole, R.; Vellis, Jean de

doi:10.1016/0169-328x(91)90128-k

Cited by 89 publications

(54 citation statements)

References 16 publications

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“…Stress responses are also cell type-specific. The observed A␤42 effect on Hsp70 expression levels in neurons but not in glia seems to be A␤-specific, because in other stress situations Hsp70 is weakly induced in nerve cells and highly upregulated in glial cells (Nishimura et al, 1991;Satoh and Kim, 1994). Interestingly, the rapid upregulation of Hsp70, as early as 6 hr, corresponded to detectable but low levels of A␤ at this time point.…”

Section: Discussionmentioning

confidence: 95%

Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed β-Amyloid in Neurons

Magrané

Smith²,

Walsh³

et al. 2004

J. Neurosci.

226

187

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Intracellular ␤-amyloid 42 (A␤42) accumulation is increasingly recognized as an early event in the pathogenesis of Alzheimer's disease (AD). We have developed a doxycycline-inducible adenoviral-based system that directs intracellular A␤42 expression and accumulation into the endoplasmic reticulum of primary neuronal cultures in a regulated manner. A␤42 exhibited a perinuclear distribution in cell bodies and an association with vesicular compartments. Virally expressed intracellular A␤42 was toxic to neuronal cultures 24 hr after induction in a dose-dependent manner. A␤42 expression prompted the rapid induction of stress-inducible Hsp70 protein in neurons, and virally mediated Hsp70 overexpression rescued neurons from the toxic effects of intracellular A␤ accumulation. Together, these results implicate the cellular stress response as a possible modulator of A␤-induced toxicity in neuronal cultures.

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Section: Discussionmentioning

confidence: 95%

Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed β-Amyloid in Neurons

Magrané

Smith²,

Walsh³

et al. 2004

J. Neurosci.

226

187

View full text Add to dashboard Cite

show abstract

“…While these studies and those from yeast, fruit flies, and plants corroborate the central features of the heat shock response, there have been a number of observations which indicate that certain tissues or cell lines exhibit a diminished or restricted response to physiological stress (10)(11)(12)(13)(14). The common observation is the deficient transcriptional induction of the gene encoding the major heat shock protein, hsp70.…”

mentioning

confidence: 75%

Deficient induction of human hsp70 heat shock gene transcription in Y79 retinoblastoma cells despite activation of heat shock factor 1.

Mathur

Sistonen

Brown

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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One ofthe basic features of the inducible heat shock response is the activation of heat shock factor which results in the rapid transcriptional induction of the heat shock genes. Although it is widely considered that the heat shock response is ubiquitous, several reports have indicated that the transcriptional response can vary in both intensity and kinetics and often in a tissue-specific manner. Of interest have been studies on the expression of heat shock genes in the brain, particularly observations that certain cultured neuronal cells exhibit a diminished heat shock response. We demonstrate that transcription of the gene encoding a 70-kDa heat shock protein (hsp7O) is diminished upon heat shock in Y79 human retinoblastoma cells (which are of neuronal origin) despite both the activation of heat shock factor 1 and induced transcription of another heat shock gene, hsp90a. This uncoupling of stressinduced transcription ofthe hsp7O and hsp9Oa genes, which are typically coordinately regulated in response to stress, appears to be due to the selective inability of trans-acting factors, including heat shock factor 1, to bind in vivo to the hsp7O promoter as the result of a chromatin-mediated effect.

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“…Notably, in this experiment geldanamycin was used in the same concentration that restored the stress-induced expression of Hsp72. Additional proof of an impaired function of Hsp90 in ScN2a cells was obtained by analyzing the activation pathway of the glucocorticoid receptor, which is regulated similarly to HSF1 (65). After transfection of a GRE-Luc reporter construct, stimulation of the endogenous glucocorticoid receptor by dexamethasone resulted in a more than 55-fold luciferase activity in N2a cells, whereas in ScN2a cells luciferase activity was increased only 9-fold (Fig.…”

Section: Scrapie-infected N2a Cells Do Not Express Inducible Hsp72 Anmentioning

confidence: 99%

Geldanamycin Restores a Defective Heat Shock Responsein Vivo

Winklhofer

Reintjes

Hoener

et al. 2001

Journal of Biological Chemistry

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Induced expression of heat shock proteins (Hsps) plays a central role in promoting cellular survival after environmental and physiological stress. We have previously shown that scrapie-infected mouse neuroblastoma (ScN2a) cells fail to induce the expression of Hsp72 and Hsp28 after various stress conditions. Here we present evidence that this impaired stress response is due to an altered regulation of HSF1 activity. Upon stress in ScN2a cells, HSF1 was converted into hyperphosphorylated trimers but failed to acquire transactivation competence. A kinetic analysis of HSF1 activation revealed that in ScN2a cells trimer formation after stress was efficient, but disassembly of trimers proceeded much faster than in the uninfected cell line. Geldanamycin, a Hsp90-binding drug, significantly delayed disassembly of HSF1 trimers after a heat shock and restored stressinduced expression of Hsp72 in ScN2a cells. Heat-induced Hsp72 expression required geldanamycin to be present; following removal of the drug ScN2a cells again lost their ability to mount a stress response. Thus, our studies show that a defective stress response can be pharmacologically restored and suggest that the HSF1 deactivation pathway may play an important role in the regulation of Hsp expression.

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Comparison of the heat shock response in cultured cortical neurons and astrocytes

Cited by 89 publications

References 16 publications

Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed β-Amyloid in Neurons

Heat Shock Protein 70 Participates in the Neuroprotective Response to Intracellularly Expressed β-Amyloid in Neurons

Deficient induction of human hsp70 heat shock gene transcription in Y79 retinoblastoma cells despite activation of heat shock factor 1.

Geldanamycin Restores a Defective Heat Shock Responsein Vivo

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