Role of ion flux in the control of c-fos expression

Morgan, James I.; Curran, Tom

doi:10.1038/322552a0

Cited by 974 publications

(389 citation statements)

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“…Calcium entry into neurons has been associated with the induction of c-fos (Morgan and Curran, 1986). We and others have observed calcium accu mulation in cortex, hippocampus, and thalamus af ter lateral fluid-percussion brain injury (Cortez et aI.…”

Section: Discussionmentioning

confidence: 89%

Regional Induction of c-Fosand Heat Shock Protein-72 mRNA following Fluid-Percussion Brain Injury in the Rat

Raghupathi

Welsh

Lowenstein

et al. 1995

J Cereb Blood Flow Metab

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Summary:To evaluate the cellular response to traumatic brain injury, the expression of mRNA for c-fos and the 72-kDa heat shock protein (hsp72) was determined using in situ hybridization following lateral fluid-percussion in jury (2.2-2.4 atm) in rat brain. At 2 h after injury, induc tion of c-fos mRNA was observed throughout the cortex ipsilateral to the site of injury, while increased expression of hsp72 mRNA was restricted to regions of the cortex surrounding the contusion area. An increase in c-fos mRNA, but not hsp72 mRNA, was observed bilaterally in the CA 3 subfield of the hippocampus and the granule cells of the dentate gyrus and in the thalamus ipsilateral to the impact site. By 6 h, increased expression of c-fos mRNA A wide range of pathologic stressors to the brain, including mechanical injury (Dragunow and Robert son, 1988;Brown et al. , 1989), ischemia (Nowak, 1990; Welsh et ai. , 1992), and seizures (Lowenstein et ai. , 1990; Morgan and Curran, 199 1a), induce the expression of immediate early genes (lEGs) and heat shock proteins. lEGs such as c-fos and jun function as transcription factors and may mediate the long-term adaptive response of neurons to acute stimuli (Morgan and Curran, 199 1b). In contrast, heat shock proteins may simply serve as markers of a generalized stress response (Gonzalez et al. , 1989;Nowak, 1990). Although lEGs and heat shock pro teins have been extensively studied in models of Received March 22, 1994; final revision received October 6, 1994; accepted October 14, 1994 Abbreviations used: CSD, cortical spreading depression; hsp72 , 72-kDa heat shock protein; lEG, immediate early gene; NGF, nerve growth factor; TBI, traumatic brain injury. 467was observed only in the corpJ,lS callosum on the impact side; hsp72 mRNA persisted In the deep cortical layers and upper layers of the subcortical white matter below the site of maximal injury. By 24 h, both c-fos and hsp72 mRNA had returned to control levels in all regions of the brain. These results demonstrate that lateral fluid percussion brain injury triggers regionally and temporally specific expression of c-fos and hsp72 mRNA, which may be suggestive of differential neuroche ' mical alterations in neurons and glia following experimental brain injury. Key Words: Brain injury-Heat shock proteins-Immediate early genes-In situ hybridization.cerebral ischemia (Nowak, 1990; Welsh et al. , 1992), less is known about the alteration of their expression following traumatic brain injury (TBI).In a model of midline fluid percussive injury, Fos protein was found to be increased in the CAl neu rons of the hippocampus as early as 15 min follow ing injury (Phillips and Belardo, 1993). However, no data on changes in Fos expression in other brain regions were reported. Using lateral fluid percussion brain injury in the rat, we and others have observed an increase in the expression of 72-kDa heat shock protein (hsp72) mRNA (by North ern analysis) (Lowenstein et ai. , 1994) and Hsp72 protein in neuronal, glial, and endothelial cells (McIntosh ...

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Section: Discussionmentioning

confidence: 89%

Regional Induction of c-Fosand Heat Shock Protein-72 mRNA following Fluid-Percussion Brain Injury in the Rat

Raghupathi

Welsh

Lowenstein

et al. 1995

J Cereb Blood Flow Metab

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“…Spreading depression is characterized by recurrent waves of neuronal depo larization, accompanied by a transient influx of cal cium (Kraig and Nicholson, 1978). Expression of c-fos is regulated, in part, by calcium influx through voltage-sensitive channels (Morgan and Curran, 1986). Thus, spreading depression-induced calcium influx could easily explain the widespread expres sion of c-fos, in both sham-operated and MCA occluded animals.…”

Section: Discussionmentioning

confidence: 99%

Regional Expression of Heat Shock Protein-70 mRNA and c-Fos mRNA following Focal Ischemia in Rat Brain

Welsh

Moyer

Harris

1992

J Cereb Blood Flow Metab

172

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Summary: In situ hybridization was used to estimate re gional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was in creased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distri bution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (l-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h Cerebral ischemia induces increased synthesis of a number of specific proteins, despite an overall reduction in the rate of protein synthesis (Kleihues and Hossmann, 1971; Dienel et aI., 1980 Dienel et aI., , 1986Nowak, 1985). Several of the induced proteins are members of a group of "heat shock" or "stress" proteins that are expressed in the central nervous system following a number of stresses, including heat shock (Brown and Rush, 1990), trauma (Gower et aI., 1989), as well as ischemia. Although the func tion of the stress proteins is not well understood, their induction has been correlated with increased resistance to injury in many cell types (for review, see Lindquist and Craig, 1988). In brain, induction of stress proteins prior to an episode of cerebral 204without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide spread increase in HSP-70 mRNA suggests that reperfu sion triggered expression in all previously ischemic re gions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the isch emic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions un dergoing injury, but is transient in surrounding regions that recover. Key Words: Heat shock protein-70--c-fos Focal ischemia-In situ hybridization-Messenger ribo nucleic acid-Middle cerebral artery.

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“…In other studies, lindane and the a and {3 isomers of hexachlorocyclohexane have been reported to produce both time· and dose-related increases in free intracellular calcium in a neurohybridoma cell line 11 • Lindane may thus exert its neurotoxic effects in part by affecting calcium homeostasis in neurons 10 • 33 • Increases in levels of intracellular free calcium can also bring about rapid and profound changes in numerous cellular processes like protein phosphorylation and gene transcription. One of the earliest transcriptionally activated genes is the fos proto-oncogene 16 • c-fos, together with other genes, is rapidly induced after cell activation, and is thought to take part in the early cellular response to a wide range of stimuli. Such genes may function as third messengers within an intracellular cascade linking extracellular stimuli to long-term adaptive processes 6 • Some of these so-called early genes are components of known transcription regulation complexes 23 and thus may be directly responsible for alterations in the expression of other target genes.…”

Section: Introductionmentioning

confidence: 99%

c-fos and ornithine decarboxylase gene expression in brain as early markers of neurotoxicity

Vendrell¹,

Zawia

Serratosa³

et al. 1991

Brain Research

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An increase of pro to-oncogene c·f os expression in cerebral cortex of rats treated with subconvulsant doses of the pesticide organochlorine lindane (y-hexachlorocyclohexane) has been detected using Northern blots. Immunohistochemical studies show that Fos protein was already increased in neuronal nuclei 3 h after treatment. The administration of the benzodiazepine diazepam prior to lindane totally blocked the activation of this proto-oncogene expression. Parallel to this increased expression of c-fos an activation of the ornithine decarboxylase (ODC) gene and enzyme was also observed. High levels of ODC mRNA and increased enzyme activity in cortex were found in rats following lindane treatment. These changes were attenuated by prior treatment of animals with diazepam. The co-induction of c·fos and ODC suggests a potential link between the ODC/polyamine system and the short-acting proto-oncogenes in stimulus-transcription coupling events.

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Role of ion flux in the control of c-fos expression

Cited by 974 publications

References 31 publications

Regional Induction of c-Fosand Heat Shock Protein-72 mRNA following Fluid-Percussion Brain Injury in the Rat

Regional Induction of c-Fosand Heat Shock Protein-72 mRNA following Fluid-Percussion Brain Injury in the Rat

Regional Expression of Heat Shock Protein-70 mRNA and c-Fos mRNA following Focal Ischemia in Rat Brain

c-fos and ornithine decarboxylase gene expression in brain as early markers of neurotoxicity

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