The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo
| Autor: | Sabine Scarzello, Charlotte Druon, Claire Sunyach, Frédéric Checler, Marie-Victoire Guillot-Sestier |
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| Přispěvatelé: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Retinal Ganglion Cells
MESH: Signal Transduction Transcription Genetic MESH: Cell Hypoxia Apoptosis MESH: Brain-Derived Neurotrophic Factor Biochemistry MESH: Antibodies Monoclonal MESH: Dose-Response Relationship Drug MESH: Recombinant Proteins Mice 0302 clinical medicine MESH: Amyloid beta-Protein Precursor MESH: Caspase 3 Staurosporine MESH: Animals Enzyme Inhibitors MESH: Tumor Suppressor Protein p53 Cells Cultured 0303 health sciences MESH: Kinetics Caspase 3 Caspase Inhibitors Cell Hypoxia Recombinant Proteins MESH: Cell Survival MESH: Enzyme Inhibitors Biotinylation [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.drug MESH: Cells Cultured MESH: Rats Cell Survival [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Cleavage (embryo) Retinal ganglion 03 medical and health sciences MESH: Receptors Nerve Growth Factor Molecular Basis of Cell and Developmental Biology In vivo medicine Animals Humans MESH: PC12 Cells PrPC Proteins MESH: PrPC Proteins Molecular Biology MESH: Mice 030304 developmental biology MESH: Humans MESH: Nerve Growth Factors MESH: Apoptosis MESH: Transcription Genetic MESH: Receptor Nerve Growth Factor MESH: Retinal Ganglion Cells Cell Biology Molecular biology In vitro MESH: Male nervous system diseases Rats Disease Models Animal MESH: Staurosporine Tumor Suppressor Protein p53 MESH: Disease Models Animal 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2009, 284 (51), pp.35973-86. ⟨10.1074/jbc.M109.051086⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M109.051086⟩ |
| Popis: | International audience; Cellular prion protein (PrP(c)) undergoes a disintegrin-mediated physiological cleavage, generating a soluble amino-terminal fragment (N1), the function of which remained unknown. Recombinant N1 inhibits staurosporine-induced caspase-3 activation by modulating p53 transcription and activity, whereas the PrP(c)-derived pathological fragment (N2) remains biologically inert. Furthermore, N1 protects retinal ganglion cells from hypoxia-induced apoptosis, reduces the number of terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling-positive and p53-immunoreactive neurons in a pressure-induced ischemia model of the rat retina and triggers a partial recovery of b-waves but not a-waves of rat electroretinograms. Our work is the first demonstration that the alpha-secretase-derived PrP(c) fragment N1, but not N2, displays in vivo and in vitro neuroprotective function by modulating p53 pathway. It further demonstrates that distinct N-terminal cleavage products of PrP(c) harbor different biological activities underlying the various phenotypes linking PrP(c) to cell survival. |
| Databáze: | OpenAIRE |
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