Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry

Verdaguer, Ester; García-Jordá, Elvira; Canudas, Anna Maria; Domı́nguez, Esther; Jiménez, Andrés; Piccoli, David A.; Escubedo, Elena; Pallas, Jorge Camarasa Merce; Camins, Antoni

doi:10.1097/00001756-200203250-00010

Cited by 84 publications

(61 citation statements)

References 22 publications

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“…E2F1 is upregulated in neurons subjected to apoptotic stimuli in vitro 46,68,104,105,107,109 and in vivo 37 and is elevated in degenerating neurons of patients with Alzheimer disease and with Down's syndrome. 93,110 In addition, neurons treated with an E2F1 antisense 68,104 as well as neurons cultured from mice null for E2F1 107,109,[111][112][113] are at least partially protected from diverse apoptotic stimuli.…”

Section: Does E2f-dependent Gene Activation Have a Role In Neuron Death?mentioning

confidence: 99%

“…Cyclin E levels are elevated in beta-amyloid-treated cortical neurons 31 and in cultured cerebellar granule neurons induced to die by kainic acid treatment 46 or by repolarization. 27.…”

Section: Cyclin Ementioning

confidence: 99%

“…44,[51][52][53][54][55][57][58][59] There is a growing number of reports that apoptotic stimuli can induce neurons, at least in some cases, to enter S phase as indicated by BrdU incorporation, mitotic figures and markers such as the proliferating cell nuclear antigen (PCNA). 20,22,31,46,60,61 However, despite the attractive idea that inappropriately expressed cyclin B may play a role in neuron death, there are presently few experimental findings to support this. As reviewed below, the best support at present comes from the cerebellar granule repolarization model in which cdk1, a cyclin B-activated cdk, has been implicated.…”

Section: Cyclin Bmentioning

confidence: 99%

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Cell cycle molecules and vertebrate neuron death: E2F at the hub

2003

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Vertebrate neuron cell death is both a normal developmental process and the catastrophic outcome of nervous system trauma or degenerative disorders. Although the mechanisms of such death include an evolutionarily conserved core apoptotic pathway that is highly homologous to that first described by Horvitz and co-workers in Caenorhabditis elegans, it appears that many instances of neuron death additionally require the transcription-dependent induction of proapoptotic molecules. One such proapoptotic transcriptional pathway revealed by studies over the past decade revolves about the transcription factor E2F and those molecules that either regulate E2F activity or that are direct or indirect transcriptional targets of E2F. Many of the molecules associated with the E2F apoptotic pathway in postmitotic neurons also participate in the cell cycle in proliferating cells. Observations in human material and in animal and cell culture models show widespread correlation between changes in expression, activity and subcellular localization of E2F-related cell cycle molecules and developmental and catastrophic neuron death. A variety of experimental approaches support a causal role for such changes in the death process and are beginning to indicate how the neuronal E2F pathway activates the core apoptotic machinery. The discovery and elaboration of the neuronal apoptotic E2F pathway provides abundant targets as well as small molecule candidates for potential therapeutic intervention in nervous system trauma and degenerative disease.

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Section: Does E2f-dependent Gene Activation Have a Role In Neuron Death?mentioning

confidence: 99%

“…Cyclin E levels are elevated in beta-amyloid-treated cortical neurons 31 and in cultured cerebellar granule neurons induced to die by kainic acid treatment 46 or by repolarization. 27.…”

Section: Cyclin Ementioning

confidence: 99%

Section: Cyclin Bmentioning

confidence: 99%

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Cell cycle molecules and vertebrate neuron death: E2F at the hub

2003

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“…Primary cultures of CGNs were prepared from postnatal day 7 Sprague-Dawley rat pups as described previously (Verdaguer et al, 2002). Cells were dissociated in the presence of trypsin and DNase I and plated in poly-L-lysine (100 g/ml)-coated dishes at a density of 8ϫ10 5 cells/cm 2 in basal Eagle's medium supplemented with 10% heat-inactivated fetal bovine serum, 0.1 mg/ml gentamicin, 2 mM L-glutamine, and 25 mM KCl.…”

Section: Cell Culturesmentioning

confidence: 99%

Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons

et al. 2007

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the antioxidant vitamin E (vit E) increases neuronal cell viability and attenuates apoptosis induced by MPP؉ . Moreover, the expression levels of cyclin D and E2F-1 induced by this parkinsonian neurotoxin were also attenuated by vit E. Since, the broad-spectrum caspase inhibitor zVAD-fmk did not attenuate MPP ؉ -induced apoptosis in CGNs, our data provide a caspase-independent mechanism mediated by neuronal reentry in the cell cycle and increased expression of the pro-apoptotic transcription factor E2F-1. Our results also suggest a potential role of oxidative stress in neuronal reentry in the cell cycle mediated by MPP ؉ . Finally, our data further support the therapeutic potential of flavopiridol, for the treatment of Parkinson's disease.

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“…(7,8) That any de novo cycling might occur in mature neurons, much less lead to their degeneration directly challenged the notion that the neuron is the prototypical post-mitotic cell, fully differentiated and nonreplicating to its death. Subsets of neurons are now known to have a basal replicative potential (9) or to reactivate cell-cycle activity in response to certain triggers of neuronal apoptosis, including growth factor withdrawal, (10) excitotoxicity, (11,12) and genotoxic stress. (13) Clinical evidence for the association between unscheduled cell-cycle activity and neuronal apoptosis includes the detection, by fluorescence in situ hybridization, of replicated DNA at certain chromosomal loci in hippocampal neurons affected by Alzheimer disease.…”

Section: Introductionmentioning

confidence: 99%

Tumorigenesis and neurodegeneration: two sides of the same coin?

Staropoli

2008

BioEssays

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SummaryDysregulation of genes that control cell-cycle progression and DNA repair is a hallmark of tumorigenesis. It is becoming increasingly apparent, however, that these defects also contribute to degeneration of post-mitotic neurons under certain conditions. The gene for ataxiatelangiectasia mutated (ATM) is a prototype for this dual mechanism of action, with loss-of-function mutations causing not only selective degeneration of cerebellar neurons but also increased susceptibility to breast cancer and hematologic malignancy. Increased dosage of amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia of Alzheimer type and may also contribute to acute leukemia and transient myeloproliferative disorder. The gene parkin, loss-of-function mutations in which account for about half of cases of early-onset Parkinson disease, has been identified as a candidate tumor suppressor gene by several groups. Parkin is deleted or downregulated in several tumor types, and its re-expression sensitizes derivative cell lines to inhibitors of cell-cycle progression. The overlap of molecular pathways implicated in cancer and neurodegeneration challenges long-held notions about differentiated cellular states and may open the door to novel therapeutic approaches to both groups of disorders.

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Kainic acid-induced apoptosis in cerebellar granule neurons: an attempt at cell cycle re-entry

Cited by 84 publications

References 22 publications

Cell cycle molecules and vertebrate neuron death: E2F at the hub

Cell cycle molecules and vertebrate neuron death: E2F at the hub

Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons

Tumorigenesis and neurodegeneration: two sides of the same coin?

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