Differential NF‐κB regulation of <i>bcl‐x</i> gene expression in hippocampus and basal forebrain in response to hypoxia

Qiu, Jingxin; Grafe, Marjorie R.; Schmura, S M; Glasgow, Joel N.; Kent, Thomas A.; Rassin, David K.; Perez‐Polo, J. Regino

doi:10.1002/jnr.1070

Cited by 50 publications

(40 citation statements)

References 47 publications

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“…We cannot currently explain why LPS exposure results in a differential response in NF‐κB subunit activation in different brain regions. In line with our findings, however, is a report of a differential response of NF‐κB regulation of gene expression in the hippocampus and basal forebrain in response to hypoxia (Qiu et al, 2001). In our study we were not able to distinguish between the response of neurons and glia to LPS exposure but it has been suggested that activation of NF‐κB in neurons protects them against degeneration whereas activation of NF‐κB in microglia promotes neuronal degeneration (Mattson and Camandola, 2001).…”

Section: Discussionsupporting

confidence: 93%

Activation of NF-κB transcription factor in the preterm ovine brain and placenta after acute LPS exposure

et al. 2006

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Intrauterine infection may be causally related to inflammation and injury of the fetal brain, however the mechanisms by which this occurs are unclear. We have investigated whether nuclear factor (NF)-kappaB, a transcription factor for proinflammatory cytokines, is activated in the fetal brain after acute LPS-exposure. At 95 days of gestation (term = approximately 147 days), 5 fetuses received a single intravenous bolus dose of LPS (1 microg/kg); 6 fetuses served as controls. Fetal blood samples were taken hourly for 6 hr post LPS-exposure to assess physiological status. Ewes and fetuses were then euthanased, placental and brain tissue examined histologically, and NF-kappaB activation assessed in several regions of the fetal brain using an electromobility shift assay (EMSA). Oxidative stress was measured using lipid peroxidation and 8-isoprostane biochemical assays and brain cytokine concentrations analysed by enzyme linked immunosorbent assay (ELISA). LPS-exposed fetuses (relative to controls) were hypoxemic and the haematocrit and lactate levels had increased. In the brains of LPS-exposed fetuses compared to controls, NF-kappaB binding activity was elevated in the hippocampus and the thalamus/basal ganglia; 8-isoprostane levels were elevated overall (P < 0.05) in the parietal/occipital/temporal lobes and thalamus/basal ganglia. TNF-alpha and IL-6 concentrations were not elevated, however, there was a tendency for an elevation of IFN-gamma concentrations in the thalamus/basal ganglia. IFN-gamma concentration was elevated (P < 0.05) in the plasma 4 hr after LPS-exposure. In the placenta, NF-kappaB binding activity was increased (P < 0.05). We conclude that acute systemic administration of LPS leads to increased binding activity of NF-kappaB subunits in specific regions of the fetal brain and in the placenta, but that there is no clear-cut relationship between this elevation and vulnerability to endotoxic damage.

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Section: Discussionsupporting

confidence: 93%

Activation of NF-κB transcription factor in the preterm ovine brain and placenta after acute LPS exposure

et al. 2006

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“…The p50/cRel activation appeared to be areaspecific and correlated with increased Bcl-X L expression and higher neuronal resistance to hypoxic insult. 80 Indeed, we found that the silencing of c-Rel abolished the increases of both MnSOD and Bcl-X L induced by CHPG. Besides, the silencing of Bcl-X L suppressed the neuroprotective activity of CHPG.…”

Section: Discussionmentioning

confidence: 73%

NF-κB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid β-peptide toxicity

et al. 2005

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Opposite effects of nuclear factor-jB (NF-jB) on neuron survival rely on activation of diverse NF-jB factors. While p65 is necessary for glutamate-induced cell death, c-Rel mediates prosurvival effects of interleukin-1b. However, it is unknown whether activation of c-Rel-dependent pathways reduces neuron vulnerability to amyloid-b (Ab), a peptide implicated in Alzheimer's disease pathogenesis. We show that neuroprotection elicited by activation of metabotropic glutamate receptors type 5 (mGlu5) against Ab toxicity depends on cRel activation. Ab peptide induced NF-jB factors p50 and p65. The mGlu5 agonists activated c-Rel, besides p50 and p65, and the expression of manganese superoxide dismutase (MnSOD) and Bcl-X L . Targeting c-Rel expression by RNA interference suppressed the induction of both antiapoptotic genes. Targeting c-Rel or Bcl-X L prevented the prosurvival effect of mGlu5 agonists. Conversely, c-Rel overexpression or TATBcl-X L addition rescued neurons from Ab toxicity. These data demonstrate that mGlu5 receptor activation promotes a c-Reldependent antiapoptotic pathway responsible for neuroprotection against Ab peptide.

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“…However, the inclusion of c-Rel as part of NFκB dimers can reportedly provide a neuroprotective effect. In this case, anti-apoptotic genes such as manganese superoxide dismutase, Bcl-XL and Bfl-1 are direct transcriptional targets of c-Rel protein 68–72…”

Section: Discussionmentioning

confidence: 99%

Glutamate-Induced NFκB Activation in the Retina

Fan

Cooper

2009

Invest. Ophthalmol. Vis. Sci.

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Purposes To determine the distribution and glutamate-mediated activation of NFκB members in the retina and pan-purified retinal ganglion cells (RGCs), and to characterize steps in the signal transduction events which lead to NFκB activation. Methods Expression patterns in the retina and RGCs were evaluated for five NFκB proteins with the aid of immunohistochemistry. Retinal explants or RGCs were treated with glutamate with or without the presence of the NDMA receptor antagonist, memantine, the calcium chelator, EGTA, or a specific inhibitor for CaMKII. Characterizations of NFκB activation were performed with the aid of electrophoretic mobility shift assays, and super shift assays. Results All five NFκB proteins were present in the retina and in the pan-purified RGCs. In response to a glutamate stimulus, all NFκB proteins except c-Rel were activated. P65 was unique in that it was not constitutively active but showed a glutamate-inducible activation in the retina and in the cultured RGCs. Memantine, or EGTA, or AIP inhibited NFκB activation in the retina. Furthermore, AIP significantly reduced the level of glutamate-induced degradation of IκBs. Conclusions These data indicate that glutamate activates distinct NFκB proteins in the retina. P65 activation may be especially important with regard to RGC responses to glutamate, given that its activity is induced by conditions which are known to lead to death of these cells. The NMDA receptor-Ca2+-CaMKII signaling pathway is involved in glutamate-induced NFκB activation. Since AIP blocks the degradation of IκB, its regulation is clearly downstream of CaMKII.

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Differential NF‐κB regulation of bcl‐x gene expression in hippocampus and basal forebrain in response to hypoxia

Cited by 50 publications

References 47 publications

Activation of NF-κB transcription factor in the preterm ovine brain and placenta after acute LPS exposure

Activation of NF-κB transcription factor in the preterm ovine brain and placenta after acute LPS exposure

NF-κB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid β-peptide toxicity

Glutamate-Induced NFκB Activation in the Retina

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