Promotion of cell death or neurite outgrowth in PC-12 and N2a cells by the fungal alkaloid militarinone A depends on basal expression of p53

Küenzi, Peter; Kiefer, Sabine; Koryakina, Anna; Hamburger, Matthias

doi:10.1007/s10495-008-0185-x

Cited by 19 publications

(18 citation statements)

References 51 publications

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“…We used two independent approaches to inhibit p53: pharmacologic inhibition with PFT-a and siRNA gene knockdown. The concentration of PFT-a was chosen based on previous reports in the literature using cardiac (51) and neural cells (52). Both pharmacologic inhibition and siRNA-mediated gene silencing of p53 yielded similar results.…”

Section: Discussionmentioning

confidence: 99%

Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Suzuki¹,

Yamashita²,

Zemans³

et al. 2009

Am J Respir Cell Mol Biol

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Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-kB, and the protooncogene p53 in this pathway. Elastase-induced apoptosis of lung epithelial cells correlated temporally with activation of NF-kB, phosphorylation, and nuclear translocation of p53, increased p53 up-regulated modulator of apoptosis (PUMA) expression, and mitochondrial translocation of Bax resulting in enhanced permeability. Elastase-induced apoptosis was also prevented by pharmacologic inhibitors of NF-kB and p53 and by short interfering RNA knockdown of PAR-1, p53, or PUMA. These inhibitors prevented elastase-induced PUMA expression, mitochondrial translocation of Bax, increased mitochondrial permeability, and attenuated apoptosis. NF-kB inhibitors also reduced p53 phosphorylation. We conclude that elastase-induced apoptosis of lung epithelial cells is mediated by a PAR-1-triggered pathway involving activation of NF-kB and p53, and a PUMA-and Baxdependent increase in mitochondrial permeability leading to activation of distal caspases. Further, p53 contributes to elastaseinduced apoptosis by both transcriptional and post-transcriptional mechanisms.

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Section: Discussionmentioning

confidence: 99%

Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Suzuki¹,

Yamashita²,

Zemans³

et al. 2009

Am J Respir Cell Mol Biol

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“…Numerous signaling pathways involving in neurite outgrowth have been proposed [2,5]. Among them, ERK and Akt activations have long been known to be important for neurite elongation induced by certain neurotrophic factors including NGF [28,29], neurotrophin-3 (NT-3) [30], BDNF [31] as well as natural compounds including FK506 [32,33], genipin [34], honokiol [4] and militarinone A [9]. In addition, ginsenoside, triterpenoidglycoside from gingseng, has been shown to significantly increase the neurite outgrowth of neuroblastoma cells [35].…”

Section: Discussionmentioning

confidence: 99%

“…Several neurotrophic ligands for tyrosine kinase receptors such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been identified [7,8]. The activation of MEK/ERK and PI3K/Akt results in an increase in cell survival as well as an enhancement of neuronal growth and differentiation [9,10]. In this context, molecules or compounds that exhibit potent neurotrophic activity are of great interest and may be useful for the treatment of stroke, brain or spinal cord injury and neurodegenerative diseases [11-13].…”

Section: Introductionmentioning

confidence: 99%

Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells

Wanakhachornkrai

Pongrakhananon

Chunhacha

et al. 2013

BMC Complement Altern Med

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BackgroundIn order to gain insight into neuroprotective effects of ECa 233, a standardized extract of Centella asiatica, previously demonstrated in animal models of memory impairment induced by transient global ischemia or intracerebroventricular injection of β-amyloid, the effect of ECa 233 on neurite outgrowth of human IMR-32 neuroblastoma cell line was investigated.MethodsCells were seeded and incubated with various concentrations of ECa 233. Morphometric analysis was carried out by a measurement of the longest neurite growth of cells at 24 and 48 h. Contributing signaling pathways possibly involved were subsequently elucidated by western blot analysis.ResultsWhile ECa 233 had only limited effects on cell viability, it significantly enhanced neurite outgrowth of IMR-32 cells at the concentrations of 1–100 μg/ml. Western blot analysis revealed that ECa 233 significantly upregulated the level of activated ERK1/2 and Akt of the treated cells suggesting their involvement in the neuritogenic effect observed, which was subsequently verified by the finding that an addition of their respective inhibitors could reverse the effect of ECa 233 on these cells.ConclusionsThe present study clearly demonstrated neurite outgrowth promoting activity of ECa 233. ERK1/2 and Akt signaling pathways seemed to account for the neurotrophic effect observed. In conjunction with in vivo neuroprotective effect of ECa 233 previously reported, the results obtained support further development of ECa 233 for clinical use in neuronal injury or neurodegenerative diseases.

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“…Different agents can promote differential gene expression in the same cell line and exhibit synergistic effects on neurite outgrowth [21]. It should also be pointed out that the same agents can cause the opposite effect in different types of neurons [22], as dissimilar as differentiation or death depending on the cell line [23].…”

Section: Cellular Models In Developmental Neurobiologymentioning

confidence: 99%

Novel Aspects of Neuronal Differentiation In Vitro and Monitoring with Advanced Biosensor Tools

Valero

Kintzios

2011

CMC

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Neuronal differentiation is a very complex and sophisticated cellular process that encompasses the development of mature neurons and their specialization. In this review we will focus on the novel and less well-known aspects of neuronal differentiation. Cell lines, to which some pro-differentiation drugs are added, have been widely used because of their convenience in terms of cost-efficiency, ease of use and reproducibility. After a brief overview of these systems, this review focuses on the new pharmacological aspects of differentiation related to mitochondrial changes and cellular redox homeostasis. A number of different parameters are commonly evaluated to assess neuronal differentiation. These include neurite length, differential gene expression, mitochondrial mass, free radical levels, enzyme induction and others. However, the classical techniques used to detect neuronal differentiation (such as immunochemistry, flow cytometry and gene expression analysis) are time-consuming or dependent on the subjective view of the researcher. On the other hand, emerging novel, miniaturized biosensor technologies have the potential to revolutionize the study of neuronal differentiation, by detecting neuron-derived electrical signals and differentiation markers, such as shape or attachment in a non-invasive and high throughput fashion. These state-of-the-art technologies are being extensively reviewed. Emphasis is given to progress, made in the field of integrated systems (including impedance sensing, microfluidics and associated nanotechnologies), neuronal differentiation in 3-D cultures and the identification of novel agents controlling neuronal cell fate.

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Promotion of cell death or neurite outgrowth in PC-12 and N2a cells by the fungal alkaloid militarinone A depends on basal expression of p53

Cited by 19 publications

References 51 publications

Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Leukocyte Elastase Induces Lung Epithelial Apoptosis via a PAR-1–, NF-κB–, and p53-Dependent Pathway

Neuritogenic effect of standardized extract of Centella asiatica ECa233 on human neuroblastoma cells

Novel Aspects of Neuronal Differentiation In Vitro and Monitoring with Advanced Biosensor Tools

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