NR ACOP
AU Chiarini,L.B.; Freitas,A.R.O.; Zanata,S.M.; Brentani,R.R.; Martins,V.R.; Linden,R.
TI Cellular prion protein transduces neuroprotective signals
QU EMBO Journal 2002 Jul 1; 21(13): 3317-26
PT journal article
AB To test for a role for the cellular prion protein (PrPc) in cell death, we used a PrPc-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 PrPc-null mice. Neuroprotection was abolished by treatment with phosphatidylinositol-specific phospholipase C, with human peptide 106-126, with certain antibodies to PrPc or with a PKA inhibitor, but not with a MEK/Erk inhibitor. In contrast, antibodies to PrPc that increased cAMP also induced neuroprotection. Thus, engagement of PrPc transduces neuroprotective signals through a cAMP/PKA-dependent pathway. PrPc may function as a trophic receptor, the activation of which leads to a neuroprotective state.
MH Animal; Animals, Newborn; Anisomycin/antagonists & inhibitors/*pharmacology; Antibodies, Monoclonal/pharmacology; Apoptosis/*drug effects/physiology; 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; Flavones/pharmacology; Forskolin/pharmacology; Gene Expression Regulation, Developmental; Immune Sera; MAP Kinase Signaling System/*drug effects; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogen-Activated Protein Kinases/drug effects/metabolism; Neurons/drug effects/metabolism; Organ Culture; Peptide Fragments/immunology/metabolism; Phospholipase C/pharmacology; Phosphoprotein Phosphatase/antagonists &; inhibitors/biosynthesis/immunology/*physiology; Phosphorylation; Protein Processing, Post-Translational; Rats; Rats, Inbred Strains; Retina/*drug effects/metabolism; Signal Transduction/*drug effects; Support, Non-U.S. Gov't; Thionucleotides/pharmacology; p42 MAP Kinase/drug effects/metabolism
AD Instituto de Biofisica da UFRJ, CCS, bloco G, Cidade Universitaria, 21949-900, Rio de Janeiro, Brasil.
SP englisch
PO England