edoc

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

Kueenzi, P. and Kiefer, S. and Koryakina, A. and Hamburger, M.. (2008) 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. Apoptosis, 13 (3). pp. 364-376.

[img]
Preview
PDF - Published Version
761Kb

Official URL: http://edoc.unibas.ch/dok/A5251066

Downloads: Statistics Overview

Abstract

The fungal alkaloid militarinone A (MiliA) was recently found to stimulate neuronal outgrowth in PC-12 cells by persistant activation of pathways that are also involved in NGF-mediated differentiation, namely the PI3-K/PKB and the MEK/ERK pathways. Application of equal concentrations of MiliA to other cells such as the murine neuroblastoma cell line N2a resulted in immediate onset of apoptosis by nuclear translocation of apoptosis inducing factor (AIF), activation of caspases and c-Jun/AP-1 transcription factor without an intermediate differentiated phenotype, although minor transient phosphorylation of PKB and MAPK as well as activation of NF-kappaB were also observed. Translocation of AIF was preceded by p53 phosphorylation at Ser15 and blocked by pifithrin alpha, a known inhibitor of p53-transcriptional activity. We here show that both cell types activate the same pathways albeit in different time scales. This is mainly due to contrasting basal expression levels of p53, which in turn regulates expression of AIF. In PC-12 cells, continuous activation of these pathways after prolonged treatment with 40 muM MiliA first led to up-regulation of p53, phosphorylation of p53, release of AIF from mitochondria and its translocation into the nucleus. Additionally, also activation of the c-Jun/AP-1 transcription factor was observed, and PC-12 cells subsequently underwent apoptosis 48-72 h post-treatment. We report that similar pathways working on different levels are able to initially shape very divergent cellular responses.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
UniBasel Contributors:Hamburger, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:1360-8185
e-ISSN:1573-675X
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:28 Nov 2017 10:22
Deposited On:22 Mar 2012 13:30

Repository Staff Only: item control page