Involvement of GABAergic and adenosinergic systems in PrPC function associated to ...
| Full text | |
| Author(s): |
Chiarini, Luciana B.
;
Freitas, Adriana R. O.
;
Zanata, Silvio M.
;
Brentani, Ricardo R.
;
Martins, Vilma R.
[5]
;
Linden, Rafael
Total Authors: 6
|
| Document type: | Journal article |
| Source: | EMBO Journal; v. 21, n. 13, p. 3317-3326, July 2002. |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 99/07124-8 - The role of celular prion protein in physiological and pathological processes |
| Grantee: | Vilma Regina Martins |
| Support type: | Research Projects - Thematic Grants |