Localization of 70 kDa Stress Protein mRNA Induction in Gerbil Brain after Ischemia

Nowak, Thaddeus S.

doi:10.1038/jcbfm.1991.84

Cited by 198 publications

(74 citation statements)

References 64 publications

(38 reference statements)

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“…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. Nowak (1991) found that expression of hsp70 mRNA was most pronounced in hippocampal CAl neurons that fail to accumulate immunoreactive HSP70 protein and are selectively lost following transient global ischemia. However, there was no apparent discrepancy between transcription and translation following our study of transient focal ischemia.…”

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

confidence: 99%

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

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

confidence: 99%

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

185

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“…Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate.…”

Section: Introductionmentioning

confidence: 99%

“…A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late effector genes, however, has not been studied.…”

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confidence: 99%

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Liu

Salminen

et al. 1994

Annals of Neurology

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Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP-1), which transregulates the expression of several genes. To study the postischemic events related to c-fos expression, we suppressed the expression of c-fos by intraventricular infusion of an antisense Oligodeoxynucleotide (anti-rncfosr 115 ) of c-fos mRNA. The effectiveness of antirncfosr 115 was confirmed first by its capability to block in vitro c-fos mRNA translation. In vivo, after intraventricular infusion of 32 P-labeled anti-rncfosr 115 , the oligodeoxynucleotide was internalized within 6 hours and detectable also in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled Oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense Oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of antirncfosr 115 , the postischemic increase in Fos expression and AP-1 binding activity were suppressed. Specificity of the effect of anti-rncfosr 115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP-1 binding activity following focal cerebral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c-fos oligodeoxynucleotides.The molecular events of brain adaptation to injury that may underlie functional recovery after stroke remain largely undefined. Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate. Glutamate receptor-mediated activation of phospholipases and protein kinases results in the alteration of nuclear regulatory processes, including the expression of immediate early genes such as c-fos, junB, and c-jun [5,12]. The Fos, Jun, and JunB proteins have been shown to form activator protein 1 (AP-1) through a conserved dimerization domain, i.e., the leucine zipper [13]. Transcription regulator AP-1 protein binds a specific DNA motif and is believed to transactivate the expression of a number of late effector genes [14][15][16][17][18][19]. In the ischemic brain, we have previously demonstrated an increase in AP-1 binding activity [9]. A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late e...

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“…The current study does not address the question of whether such production of HSP70 by the vasculature is protective. Heat shock protein 70 is preferentially induced in injured but still viable cells (Nowak, 1991;Sloviter and Lowenstein, 1992), and there is evidence that the induction of HSP70 in endothelial cell protects it from injuries such as those induced by ischemia-reperfusion .…”

Section: T Masada Et Al 30mentioning

confidence: 99%

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Masada

Hua

et al. 2001

J Cereb Blood Flow Metab

112

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Summary: Ischemic preconditioning (IPC) induces neuroprotection to subsequent severe ischemia, but its effect on the cerebrovasculature has not been studied extensively. This study evaluated the effects of IPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebral ischemia in the rat. Transient (15 minute) middle cerebral artery occlusion (MCAO) was used for IPC. Three days after IPC or a sham operation, permanent MCAO was induced. Twenty-four hours after permanent MCAO, neurologic deficit, infarction volume, and water and ion content were evaluated. Six hours post-ischemia, blood-brain barrier (BBB) permeability was examined using [ 3 H]-inulin. Water, ion contents, and BBB permeability were assessed in three zones (core, intermediate, and outer) depending on their relation to the MCA territory. Heat shock protein 70 (HSP70) was also examined as a potential marker of vascular injury. The model of IPC significantly reduced brain infarction and neurologic deficit. Compared with a sham operation, IPC also significantly attenuated brain edema formation in the intermediate (sham and IPC water contents: 5.99 ± 0.65 vs. 4.99 ± 0.81 g/g dry weight; P < 0.01) and outer zones (5.02 ± 0.48 vs. 4.37 ± 0.42 g/g dry weight; P < 0.01) of the ipsilateral hemisphere but not in the core zone. Blood-brain barrier disruption assessed by [ 3 H]-inulin was significantly attenuated in the IPC group and the number of blood vessels that displayed HSP70 immunoreactivity was also reduced. Thus, IPC significantly attenuates ischemic brain edema formation, BBB disruption, and, as assessed by HSP70, vascular injury. Understanding the mechanisms involved in IPC may provide insight into methods for preserving cerebrovascular function during ischemia. Key Words: Brain ischemia-Ischemic preconditioning-Brain edema-Blood-brain barrier-HSP70.

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Localization of 70 kDa Stress Protein mRNA Induction in Gerbil Brain after Ischemia

Cited by 198 publications

References 64 publications

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

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

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

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