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PMID: 12093733 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cellular prion protein transduces neuroprotective signals.

The EMBO journal ·Vol. 21 ·No. 13 ·2002-07-01 ·Pages 3317-26

Chiarini LB, Freitas AR, Zanata SM, Brentani RR, Martins VR, Linden R

Abstract

To test for a role for the cellular prion protein (PrP(c)) in cell death, we used a PrP(c)-binding peptide. Retinal explants from neonatal rats or mice were kept in vitro for 24 h, and anisomycin (ANI) was used to induce apoptosis. The peptide activated both cAMP/protein kinase A (PKA) and Erk pathways, and partially prevented cell death induced by ANI in explants from wild-type rodents, but not from PrP(c)-null mice. Neuroprotection was abolished by treatment with phosphatidylinositol-specific phospholipase C, with human peptide 106-126, with certain antibodies to PrP(c) or with a PKA inhibitor, but not with a MEK/Erk inhibitor. In contrast, antibodies to PrP(c) that increased cAMP also induced neuroprotection. Thus, engagement of PrP(c) transduces neuroprotective signals through a cAMP/PKA-dependent pathway. PrP(c) may function as a trophic receptor, the activation of which leads to a neuroprotective state.

MeSH Terms
Animals Animals, Newborn Anisomycin/antagonists & inhibitors,pharmacology Antibodies, Monoclonal/pharmacology Apoptosis/drug effects,physiology Colforsin/pharmacology Cyclic AMP/analogs & derivatives,pharmacology,physiology Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,drug effects,metabolism Enzyme Inhibitors/pharmacology Eye Proteins/antagonists & inhibitors,biosynthesis,immunology,physiology Flavonoids/pharmacology Gene Expression Regulation, Developmental Immune Sera MAP Kinase Signaling System/drug effects Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinase 1/drug effects,metabolism Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases/drug effects,metabolism Neurons/drug effects,metabolism Organ Culture Techniques Peptide Fragments/immunology,metabolism Phosphatidylinositol Diacylglycerol-Lyase Phosphoinositide Phospholipase C Phosphorylation PrPC Proteins/chemistry,metabolism Protein Processing, Post-Translational Rats Rats, Inbred Strains Retina/drug effects,metabolism Signal Transduction/drug effects Thionucleotides/pharmacology Type C Phospholipases/pharmacology
Chemicals
Antibodies, Monoclonal Enzyme Inhibitors Eye Proteins Flavonoids Immune Sera Peptide Fragments PrPC Proteins Thionucleotides Colforsin adenosine-3',5'-cyclic phosphorothioate Anisomycin Cyclic AMP Cyclic AMP-Dependent Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Type C Phospholipases Phosphoinositide Phospholipase C Phosphatidylinositol Diacylglycerol-Lyase 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chiarini Luciana B
Instituto de Biofísica da UFRJ, CCS, bloco G, Cidade Universitária, 21949-900, Rio de Janeiro, Brasil.
Freitas Adriana R O
Zanata Silvio M
Brentani Ricardo R
Martins Vilma R
Linden Rafael
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf324
Published
2002-07-01
Pages
3317-26
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125390
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf324 PMC Full Text View journal details
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