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Doppel-induced apoptosis and counteraction by cellular prion protein in neuroblastoma and astrocytes.
- Source :
-
Neuroscience [Neuroscience] 2006 Sep 01; Vol. 141 (3), pp. 1375-88. Date of Electronic Publication: 2006 Jun 12. - Publication Year :
- 2006
-
Abstract
- Expression of a prion-like protein, doppel, induces apoptosis-like changes in cerebellar neuronal granule and Purkinje cells of prion-knockout mice and this effect can be rescued by re-introduction of cellular prion. Since most of those studies were done in transgenic mice, in the present study, we have established a murine neuro-2a cell line and the primary rat adult reactive astrocyte model for studying doppel-induced apoptosis and possible prion counteraction. We demonstrate that expression of doppel in neuro-2a cells causes apoptosis, during which DNA fragmentation occurs as visualized by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling staining and other intracellular changes characteristic of apoptosis are observed in the electron microscope. Using immunoblot analyses, we further demonstrate that doppel expression activates caspase-10 as well as caspase-3, but does not activate caspase-9. Addition of purified doppel to cultures of neuro-2a cells and the primary astrocytes causes similar apoptotic changes. Significantly, apoptosis induced by doppel is enhanced when cellular prion protein is depleted by RNA interference, suggesting a protective effect of cellular prion against doppel-induced apoptosis. The antagonistic interaction between cellular prion and doppel appears to involve direct protein-protein interaction possibly on cell membrane as cellular prion and doppel physically interact with each other and co-localize on cell membranes. Together, our data show that doppel induces apoptosis in neuroblastoma neuro-2a and rat primary astrocytes via a caspase-10 mediated pathway and that this effect is counteracted by cellular prion through direct interaction with doppel possibly on cell membrane.
- Subjects :
- Animals
Astrocytes ultrastructure
Blotting, Western methods
Caspases metabolism
Cells, Cultured
Drug Interactions
Fluorescent Antibody Technique methods
GPI-Linked Proteins
Gene Expression drug effects
Gene Expression physiology
In Situ Nick-End Labeling methods
Indoles
Mice
Microscopy, Electron, Transmission methods
Neuroblastoma metabolism
Neuroblastoma ultrastructure
Prions metabolism
Prions pharmacology
RNA Interference physiology
Rats
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
Time Factors
Transfection methods
Apoptosis drug effects
Astrocytes drug effects
Neuroblastoma pathology
Prions physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 141
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 16766127
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2006.04.068