Focal cerebral ischaemia increases the levels of several classes of heat shock proteins and their corresponding mRNAs

Wagstaff, Marcus J. D.; Collaço‐Moraes, Yolanda; Aspey, B. S.; Coffin, Robert S.; Harrison, Michael J.; Latchman, David S.; Belleroche, Jacqueline de

doi:10.1016/s0169-328x(96)00127-1

Cited by 56 publications

(40 citation statements)

References 53 publications

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“…A number of studies have documented that HSP levels increase in the ischemic penumbra of the brain in animal models of focal ischemia, which is an area where many injured neurons survive [19] . It has been reported that gene transfer induced HSP70 overexpression protects neurons from ischemic brain damage in experimental rat stroke models [20] .…”

Section: Discussionmentioning

confidence: 99%

Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

et al. 2011

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Aim: To examine the effects of a mixed formulation composed of prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after cerebral ischemia. The effects of the mixture on protein expression of heat shock proteins (HSPs), p53, and Bcl-2 were also determined. Methods: Brain ischemia was induced with a permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were treated with a single intravenous administration of PGE1, lithium or a PGE1+Li mixture immediately after the ischemic insult. The infarct volume and motor behavior deficits were analyzed 24 h after the ischemic insult. The protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60, Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were examined using immunoblotting. Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced infarct volume and neurological deficits induced by focal cerebral ischemia. Moreover, the mixture had a greater neuroprotective effect against cerebral ischemia compared with PGE1 or lithium alone. The mixture was effective even if it was administered 3 h after ischemia. PGE1+Li also significantly upregulated cytoprotective HSP70, GRP78, HSP60, and Bcl-2 protein levels, while decreasing p53 expression. Conclusion: These results demonstrated a PGE1+Li mixture with a therapeutic window of up to 3 h for clinical treatment of cerebral ischemia. The PGE1+Li mixture potentially exerts a protective effect after stroke through the induction of HSPs and Bcl-2 proteins.

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Section: Discussionmentioning

confidence: 99%

Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

et al. 2011

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“…Thus, we have shown that overexpression of hsp27 has a similar protective effect against thermal and ischemic stress in both ND7 cells and DRG neurons, whereas hsp56 has some protective effect against both these stresses in DRG neurons but not in ND7 cells. This is of particular interest since we have previously shown that hsp70, hsp27, and hsp56 are all overexpressed during cerebral ischemia in vivo (51).…”

Section: Figmentioning

confidence: 95%

Protection of Neuronal Cells from Apoptosis by Hsp27 Delivered with a Herpes Simplex Virus-based Vector

Wagstaff

Collaco-Moraes

Smith

et al. 1999

Journal of Biological Chemistry

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203

127

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Overexpression of the gene encoding the 70-kDa heat shock protein (hsp70) has previously been shown to protect neuronal cells against subsequent thermal or ischemic stress. It has no protective effect, however, against stimuli that induce apoptosis, although a mild heat shock (sufficient to induce hsp synthesis) does have a protective effect against apoptosis. We have prepared disabled herpes simplex virus-based vectors that are able to produce high level expression of individual hsps in infected neuronal cells without damaging effects. We have used these vectors to show that hsp27 and hsp56 (which have never previously been overexpressed in neuronal cells) as well as hsp70 can protect dorsal root ganglion neurons from thermal or ischemic stress. In contrast, only hsp27 can protect dorsal root ganglion neurons from apoptosis induced by nerve growth factor withdrawal, and hsp27 also protects the ND7 neuronal cell line from retinoic acid-induced apoptosis. However, hsp70 showed no protective effect against apoptosis in contrast to its anti-apoptotic effect in non-neuronal cell types. These results thus identify hsp27 as a novel neuroprotective factor and show that it can mediate this effect when delivered via a high efficiency viral vector.The heat shock proteins (hsps) 1 were originally identified on the basis of their increased synthesis following exposure to elevated temperature. Subsequently, however, they were shown to be induced by a wide variety of other stresses in many different cell types (for review see Refs. 1-3) including neuronal cells exposed to ischemia (4), amphetamine treatment (5), or to sodium arsenite (6). Such induction of the hsps has been shown to have a protective effect against exposure to a subsequent stress in a variety of cell types. Thus, for example, exposure of primary neuronal cultures to a mild heat stress or ischemic stress sufficient to induce the hsps has been shown to be protective against subsequent exposure to the excitotoxin glutamate or to severe heat or ischemic stress (6 -8), whereas similar exposure in vivo can protect against damaging effects caused by subsequent exposure to light (9) or ischemia (10, 11).In a number of cases the protective effect of a mild hspinducing stress can be reproduced by the artificial overexpression of a single hsp. Thus, for example, dorsal root ganglion (DRG) neurons can be protected against thermal or ischemic stress by overexpression of either the 70-kDa hsp (hsp70) or the 90-kDa hsp (hsp90) (12-14), and a similar protective effect of hsp70 and hsp90 has also been observed in the ND7 immortalized cell line derived from sensory neurons (15). Interestingly, Fink et al. (16) were able to protect cultured hippocampal neurons against subsequent heat shock using a herpes simplex virus (HSV)-derived amplicon vector expressing hsp70 indicating that this effect applies to neurons derived from both the central and peripheral nervous systems. Moreover, the use of an HSV-based vector opens up the possibility of testing the protective effect of the h...

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“…The heat shock proteins (HSPs) 1 are a family of proteins originally identified as being up-regulated in response to elevated temperature, but now a wide range of cellular stresses such as hypoxia, ischemia, glutamate, and heavy metals have been shown to induce HSPs (1)(2)(3)(4)(5)(6). HSPs consist of a family of highly conserved proteins grouped according to their molecular size: the high molecular mass proteins (110, 90, 70 -72, and 55-60 kDa) and the small HSPs, which include HSP27, ubiquitin, ␣A-and ␣B-crystallin, and related species.…”

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confidence: 99%

The Neuroprotective Effects of Heat Shock Protein 27 Overexpression in Transgenic Animals against Kainate-induced Seizures and Hippocampal Cell Death

Akbar

Lundberg

et al. 2003

Journal of Biological Chemistry

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139

109

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The 27-kDa heat shock protein (HSP27) has a potent ability to increase cell survival in response to a wide range of cellular challenges. In order to investigate the mode of action of HSP27 in vivo, we have developed transgenic lines, which express human HSP27 at high levels throughout the brain, spinal cord, and other tissues. In view of the particular property of HSP27 compared with other HSPs to protect neurons against apoptosis, we have tested these transgenic lines in a well established in vivo model of neurotoxicity produced by kainic acid, where apoptotic cell death occurs. Our results demonstrate for the first time the marked protective effects of HSP27 overexpression in vivo, which significantly reduces kainate-induced seizure severity and mortality rate (>50%) in two independent lines and markedly reduces neuronal cell death in the CA3 region of hippocampus. This reduced seizure severity in HSP27 transgenic animals was associated with a marked attenuation of caspase 3 induction and apoptotic features. These studies clearly demonstrate that HSP27 has a major neuroprotective effect in the central nervous system in keeping with its properties demonstrated in culture and highlight an early stage in the cell death pathway that is affected by HSP27.The heat shock proteins (HSPs) 1 are a family of proteins originally identified as being up-regulated in response to elevated temperature, but now a wide range of cellular stresses such as hypoxia, ischemia, glutamate, and heavy metals have been shown to induce HSPs (1-6). HSPs consist of a family of highly conserved proteins grouped according to their molecular size: the high molecular mass proteins (110, 90, 70 -72, and 55-60 kDa) and the small HSPs, which include HSP27, ubiquitin, ␣A-and ␣B-crystallin, and related species. Although highly conserved across species, variation in protein size occurs; for example, the 27-kDa human HSP27 has a corresponding isoform of 25 kDa in rodents referred to as HSP25. HSPs are both constitutively expressed and induced in response to stressful stimuli (e.g. HSP27 and HSP70). Rapid induction of HSP expression is mediated by specific heat shock factors (heat shock factors 1-4), which regulate transcription (7).The HSPs play a key role in cellular defense systems, acting as protein chaperones facilitating protein folding and the removal of aberrant proteins. These properties have been shown to contribute to the enhanced cellular survival produced following preconditioning stimuli in which a subthreshold stimulus is used to raise endogenous heat shock protein levels prior to the main stimulus. Primary neuronal cultures are protected by prior exposure to mild heat or ischemic stress before subsequent more severe heat or ischemic stress or exposure to glutamate (8 -10). In cardiac tissue, a mild heat shock also protects against a subsequent thermal or ischemic stress (11).The effects of heat shock can be mimicked by overexpression of HSPs alone. Both the ND7 immortalized neuronal cell line, which is derived from dorsal root ganglia ...

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Focal cerebral ischaemia increases the levels of several classes of heat shock proteins and their corresponding mRNAs

Cited by 56 publications

References 53 publications

Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

Protection of Neuronal Cells from Apoptosis by Hsp27 Delivered with a Herpes Simplex Virus-based Vector

The Neuroprotective Effects of Heat Shock Protein 27 Overexpression in Transgenic Animals against Kainate-induced Seizures and Hippocampal Cell Death

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