Zinc toxicity and induction of the 72 kD heat shock protein in primary astrocyte culture

Swanson, Raymond A.; Sharp, Frank R.

doi:10.1002/glia.440060307

Cited by 32 publications

(14 citation statements)

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“…This suggests that at least a major part of HSP70-immunoreactive glial cells recognized in this study are astrocytes. Our findings of HSWO expression in astrocytes following seizure-induced brain injury are consistent with several other studies, namely, that HSP70 is induced in reactive astrocytes following hyperthermia (Goto et al, 1993), administration of the anticonvulsant drug valproate (Martin and Regan, 1988), high concentration of zinc (Swanson and Sharp, 1992), senile dementia or Alzheimer's disease (Harrison et al, 1993;Renkawek et aL, 1994) and other neurodegenerative diseases (Diedrich et nl., 1993), mechanical or percussive brain injury (Brown et al, 1989;Tanno et al, 1993), and transient focal cerebral ischaemia (Kinouchi et al, 1993a). These results clearly indicate that HSP70 expression in reactive astrocytes is a common astrocytic reaction in response to any type of severe brain insult.…”

Section: Hsp70 Expression In Glial Cellssupporting

confidence: 94%

Gradation of Kainic Acid‐induced Rat Limbic Seizures and Expression of Hippocampal Heat Shock Protein‐70

Zhang

Gelowitz

Lai

et al. 1997

Eur J of Neuroscience

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Systemic injection of kainic acid (KA) induces limbic seizures in rats, which resemble human temporal lobe epilepsy, the most common form of adult human epilepsy. In this study, we have investigated KA-elicited limbic seizures in the rats by correlating the severity of the seizure attacks with the expression of hippocampal heat shock protein-70 (HSP70) which has been suggested to be a marker for neuronal injury/death in this model of seizures. After a systemic injection of KA, six stages of limbic seizures have been classified, namely, staring (stage 1), wet dog shake (stage 2), hyperactivity (stage 3), rearing (stage 4), rearing and falling (stage 5), and jumping (stage 6). Stages 4, 5 and 6 were further divided into mild and severe sub-stages. HSP70 expression was not detected in animals with stages 1 and 2 seizures. At stage 3 a small amount of HSP70 immunoreactive neurons was detected in the CA3 field and the dentate hilus. From stage 4 to stage 5 the degree of HSP70 immunoreactivity increased in the CA1 field from a few positive cells in stage 4 mild to large numbers of immunoreactive neurons in stage 5 severe. HSP70 became detectable in pyramidal cells in the CA2 field from stage 5 severe and higher. In animals with stage 6 seizures, the majority of HSP70 expression became located in glial cells throughout the whole hippocampus. We concluded that HSP70 expression in the hippocampus positively correlates with the severity of KA-elicited limbic seizures.

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Section: Hsp70 Expression In Glial Cellssupporting

confidence: 94%

Gradation of Kainic Acid‐induced Rat Limbic Seizures and Expression of Hippocampal Heat Shock Protein‐70

Zhang

Gelowitz

Lai

et al. 1997

Eur J of Neuroscience

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“…, 1986), it is possible that there is some interaction between infarcted neurons and glia in the penumbra (Sharp et aI., 1991a). Swanson and Sharp (1992) have also shown that treatment of cultured astrocytes with zinc pro duces areas of astrocyte death without HSP induc tion, which are surrounded by HSP70-positive and viable astrocytes on the margins. Though the expla nation for this is uncertain, we propose that astro cytes within an infarction cannot synthesize HSP70 protein, whereas injured astrocytes at the margins of an infarction that will survive can synthesize hsp70 mRNA and HSP70 protein.…”

Section: This Induction In the Endothelial Cells In Infarcted Brain Rmentioning

confidence: 93%

Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

Kinouchi

Sharp

Hill

et al. 1993

J Cereb Blood Flow Metab

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185

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Summary: Induction of the 70-kDa heat shock protein (HSP70) was demonstrated immunocytochemically in adult rats 4 h to 7 days following temporary middle cere bral artery (MeA) occlusions lasting 30, 60, or 90 min. Maximal HSP70 induction occurred �24 h following ischemia. Thirty minutes of ischemia induced HSP70 in neurons throughout the cortex in the MeA distribution, whereas 90 min of ischemia induced HSP70 in neurons in the penumbra. HSP70 protein was induced in endothelial cells in infarcted neocortex following 60-90 min of MeA occlusion, and HSP70 was induced in endothelial cells in infarcted regions of lateral striatum following 30-90 min Normal rat brain cells do not express the 70-kDa heat shock protein (HSP70) (Vass et aI. , 1988; Brown et aI. , 1989; Gonzalez et aI. , 1989; Sharp et aI. , 1991a,b), which is a product of the hsp70 gene (Hunt and Morimoto, 1985). HSP70 is induced in brain in response to hyperthermia (Brown, 1983;Sprang and Brown, 1987; Barbe et aI. , 1988), epi lepsy (Gonzalez et aI. , 1989; Vass et aI. , 1989; Lo wenstein et aI., 1990), hypoxia-ischemia (Nowak, 1985 Kiessling et aI. , 1986; Vass et aI. , 1988; Dwy er et aI. , 1989; Gonzalez et aI., 1989; Ferriero et aI. , 1990), injection of excitotoxins (Uney et aI. , 1988; Gonzalez et aI. , 1989) 105of MeA occlusion. hsp70 mRNA was induced in the MeA distribution in cortex and to a lesser extent in stri atum at 2 h to 3 days following 60 min of ischemia. It is proposed that brief ischemia induces hsp70 mRNA and HSP70 protein in the cells most vulnerable to ischemia the neurons. HSP70 protein is not induced in most neu rons and glia following 60-90 min of ischemia in areas destined to infarct, whereas it is induced in vascular en dothelial cells. Key Words: Focal brain-hsp70 mRNA Middle cerebral artery-Stress and heat shock protein Stroke.1981; Brown et aI. , 1989). Gonzalez et al. (1989) emphasized the potential value of using HSP70 im munostaining as a sensitive marker of brain cell in jury.HSPs are a family of proteins that perform many functions. Some 60-to 80-kDa HSPs appear to chaperone protein movements across membranes and mediate important protein-protein interactions in normal and stressed cells (Chapell et aI. , 1986;Ellis, 1987; Chirico et aI. , 1988; Cheng et aI. , 1989; Chiang et aI. , 1989; Deshaies et aI. , 1989; Beck mann et aI. , 1990). Some 90-kDa HSPs regulate ste roid receptor availability.Once HSPs are induced, they may prevent pro teins from being denatured (Pelham, 1986) and pro tect cells from subsequent injury (Schlesinger et aI. , 1982;Johnston and Kucey, 1988; Riabowol et aI., 1988). Barbe et al. (1988) provided the first direct evidence for this protective role in the CNS by showing that preinduction in the rabbit retina via systemic hyperthermia is associated with a de crease in light-induced retinal injury. Moreover, mild global cerebral ischemia, sufficient to induce 106 H. KINOUCHI ET AL.HSP70 in the hippocampus, attenuates the hippo campal injury associated with a subsequent severe ischemic...

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“…Much less, however, is known about the effects of zinc on glial cells. Cellular zinc toxicity in glia was previously characterized with respect to dose and time dependence and was shown to be influenced by serum components (Choi et al, 1988;Swanson and Sharp, 1992). Under the experimental conditions used in our study, we determined that astrocytic cell death began below 200 M zinc and at ϳ300 M, there was 100% cell death.…”

Section: Zinc Is Cytotoxic For Astrocytesmentioning

confidence: 98%

“…Astrocytes, for example, regulate levels of extracellular K ϩ and are key elements in the control of the extracellular milieu of neurons (Ransom et al, 2003). Although zinc is toxic to cultured neurons already at lower concentrations compared with cultured astrocytes (Swanson and Sharp, 1992;Dineley et al, 2000), levels of zinc that are toxic to astrocytes may be reached in the brain during excitotoxic episodes (Choi and Koh, 1998;Vogt et al, 2000). Indeed, massive glial cell death was reported following ischemic insults in rats (Choi and Koh, 1998).…”

Section: Introductionmentioning

confidence: 98%

ZnT‐1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc

Nolte

Gore

Sekler

et al. 2004

Glia

102

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Zinc ions are emerging as an important factor in the etiology of neurodegenerative disorders and in brain damage resulting from ischemia or seizure activity. High intracellular levels of zinc are toxic not only to neurons but also to astrocytes, the major population of glial cells in the brain. In the present study, the role of ZnT-1 in reducing zinc-dependent cell damage in astrocytes was assessed. Zinc-dependent cell damage was apparent within 2 h of exposure to zinc, and occurred within a narrow range of approximately 200 microM. Pretreatment with sublethal concentrations of zinc rendered astrocytes less sensitive to toxic zinc levels, indicating that preconditioning protects astrocytes from zinc toxicity. Fluorescence cell imaging revealed a steep reduction in intracellular zinc accumulation for the zinc-pretreated cells mediated by L-type calcium channels. Heterologous expression of ZnT-1 had similar effects; intracellular zinc accumulation was slowed down and the sensitivity of astrocytes to toxic zinc levels was reduced, indicating that this is specifically mediated by ZnT-1 expression. Immunohistochemical analysis demonstrated endogenous ZnT-1 expression in cultured astroglia, microglia, and oligodendrocytes. Pretreatment with zinc induced a 4-fold increase in the expression of the putative zinc transporter ZnT-1 in astroglia as shown by immunoblot analysis. The elevated ZnT-1 expression following zinc priming or after heterologous expression of ZnT-1 may explain the reduced zinc accumulation and the subsequent reduction in sensitivity toward toxic zinc levels. Induction of ZnT-1 may play a protective role when mild episodes of stroke or seizures are followed by a massive brain insult.

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Zinc toxicity and induction of the 72 kD heat shock protein in primary astrocyte culture

Cited by 32 publications

References 50 publications

Gradation of Kainic Acid‐induced Rat Limbic Seizures and Expression of Hippocampal Heat Shock Protein‐70

Gradation of Kainic Acid‐induced Rat Limbic Seizures and Expression of Hippocampal Heat Shock Protein‐70

Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

ZnT‐1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc

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