Increased expression of c-fos mRNA and AP-1 transcription factors after cortical impact injury in rats

Yang, Kuo-Hsin; Mu, X. S.; Xue, Jian-Fu; Whitson, J. S.; Salminen, Antero; Dixon, C. Edward; Liu, P.K.; Hayes, Ronald L.

doi:10.1016/0006-8993(94)91964-x

Cited by 81 publications

(49 citation statements)

References 37 publications

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“…What is the probability that a full-length mRNA be transcribed from its nuclear gene with oxidative DNA lesions? One example is the expression of AP-1, a transcription factor, which is composed of proteins encoded by c-fos and/or other immediate early genes and transactivates late effector genes that are either detrimental (Hengerer et al, 1990) or salutary to cell viability (Yang et al, 1994). Under physiologic conditions, little mRNA encoding FOS is detected in the brain.…”

Section: Neurons and Terminal Differentiation Of Reperfusionmentioning

confidence: 99%

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

Schaller

Graf

2004

J Cereb Blood Flow Metab

300

208

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The ischemic penumbra has been documented in the laboratory animal as severely hypoperfused, nonfunctional, but still viable brain tissue surrounding the irreversibly damaged ischemic core. Saving the penumbra is the main target of acute stroke therapy, and is the theoretical basis behind the reperfusion concept. In experimental focal ischemia, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called reperfusion injury). Activated neutrophils contribute to vascular reperfusion damage, yet posthypoxic cellular injury occurs in the absence of inflammatory species. Protein synthesis inhibition occurs in neurons during reperfusion after ischemia, underlying the role that these pathways play in prosurvival and proapoptotic processes that may be differentially expressed in vulnerable and resistant regions of the reperfused brain tissue. Ischemia-induced decreases in the mitochondrial capacity for respiratory activity probably contribute to the ongoing impairment of energy metabolism during reperfusion and possibly also the magnitude of changes seen during ischemia. From these experimental data, the concept of single-drug intervention cannot be effective. Further experimental research is needed, especially of the study of biochemical markers of the injury process to establish the role of several drugs.

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Section: Neurons and Terminal Differentiation Of Reperfusionmentioning

confidence: 99%

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

Schaller

Graf

2004

J Cereb Blood Flow Metab

300

208

View full text Add to dashboard Cite

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“…Although large-scale expression analyses using DNA microarrays only yield mRNAs profiles without distinguishing between transcriptional regulation and post-transcriptional events, it is likely that the mRNA changes described here result in protein changes after SCI. CNS trauma-induced stimulation of mRNAs correlates well with changes in transcription factor, cytokine, and growth factor protein levels (Taupin et al, 1993;Humpel et al, 1993;Yang et al, 1994;Raghupathi and McIntosh, 1996;Holmin et al, 1997;Nesic et al, 2001). In Figure 6, there is an outline of the roles that the gene products, here identified, might have in neurodegeneration and recovery after SCI.…”

Section: Discussion Expression Profile Of the Contused Spinal Cord Onmentioning

confidence: 99%

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Nešić

Švrakić

et al. 2002

J of Neuroscience Research

102

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Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate ) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome.

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“…AP-1 is a dimer composed of various Fos and Jun family proteins (Chiu et al, 1988;Halazonetis et al, 1988). Immediate early genes of the fos and jun families are upregulated after ischemic and traumatic CNS injury Yang et al, 1994). AP-1, functioning as a proinflammatory transcription factor, transactivates a number of genes that are expressed in inflammation Wisdom, 1999).…”

mentioning

confidence: 99%

Glucocorticoid Receptor-Mediated Suppression of Activator Protein-1 Activation and Matrix Metalloproteinase Expression after Spinal Cord Injury

et al. 2001

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Post-traumatic inflammatory reaction may contribute to progressive tissue damage after spinal cord injury (SCI). Two key transcription factors, nuclear factor B (NF-B) and activator protein-1 (AP-1), are activated in inflammation. An increase in NF-B binding activity has been shown in the injured spinal cord. We report activation of AP-1 after SCI. Electrophoretic mobility shift assay showed that AP-1 binding activity increased after SCI, starting at 1 hr, peaking at 8 hr, and declining to basal levels by 7 d. Methylprednisolone (MP) is the only therapeutic agent approved by the Food and Drug Administration for treating patients with acute traumatic SCI. MP reduced posttraumatic AP-1 activation. RU486, a glucocorticoid receptor (GR) antagonist, reversed MP inhibition of AP-1 activation. Immunostaining showed an increase in the expression of the Fos-B and c-Jun components of AP-1 in the injured cord. A c-fos antisense oligodeoxynucleotide (ODN) inhibited AP-1, but not NF-B, activation after SCI. AP-1 and NF-B can transactivate genes encoding matrix metalloproteinase-1 (MMP-1) and MMP-9. Western blotting and immunostaining show increased expression of MMP-1 and MMP-9 in the injured cord. MP inhibited MMP-1 and MMP-9 expression after SCI. RU486 reversed this MP effect. The c-fos antisense ODN, however, failed to suppress MMP-1 or MMP-9 expression. These findings demonstrate that MP may suppress post-traumatic inflammatory reaction by inhibiting both the AP-1 and NF-B transcription cascades via a GR mechanism. Expression of inflammatory genes such as MMP-1 and MMP-9 that are transactivated jointly by AP-1 and NF-B may not be suppressed by inhibiting only AP-1 activity. Key words: inflammation; methylprednisolone; NF-B; protease; RU486; transcription factorMethylprednisolone (MP), a synthetic glucocorticoid (GC), is the only therapeutic agent approved by the Food and Drug Administration (FDA) for the treatment of acute traumatic spinal cord injury (SCI) in humans (Bracken, 1990). However, the effect of MP in SCI is modest (Nesathurai, 1998), and its mechanism of action remains to be fully delineated. GCs including MP are anti-inflammatory agents with a wide range of useful clinical applications (Barnes, 1998). A post-traumatic inflammatory reaction has been extensively documented in animal SCI models

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Increased expression of c-fos mRNA and AP-1 transcription factors after cortical impact injury in rats

Cited by 81 publications

References 37 publications

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition

Glucocorticoid Receptor-Mediated Suppression of Activator Protein-1 Activation and Matrix Metalloproteinase Expression after Spinal Cord Injury

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