Open AccessInvolvement of the receptor for advanced glycation-end products (RAGE) in β-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro
Author(s) -
Silvia Baiguera,
Lara Fioravanzo,
Claudio Grandi,
Rosa Di Liddo,
Pier Paolo Parnigotto,
Marcella Folin
Publication year - 2009
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm_00000199
Subject(s) - glycation , rage (emotion) , nitric oxide synthase , viability assay , receptor , nitric oxide , in vitro , chemistry , extracellular , pharmacology , microbiology and biotechnology , biology , biochemistry , endocrinology , neuroscience
To ascertain whether the potential biological effects of beta amyloid (betaA) on the endothelium are partly mediated by the receptor for advanced glycation-end products (RAGE), we performed a series of experiments which analyzed the effects of the betaA(1-42) peptide on in vitro cerebromicrovascular endothelial cells (CECs). Our results suggest that RAGE is directly responsible for betaA(1-42) actions on CECs, such as its toxic effect on cell survival, viability and angiogenic capability. We observed that a 6-h incubation period exposing CECs to betaA(1-42) increased the extracellular levels of nitrite. Furthermore, the presence of a nitric oxide synthase inhibitor, L-NAME, was able to enhance CEC survival and viability. Immunocytochemical analyses demonstrated that the peptide induced expression of the inducible form of NOS, iNOS, typically synthesized in response to immune/inflammatory stimuli. Upon blocking the interaction of betaA(1-42) and RAGE, we observed significantly decreased levels of NO and suppression of iNOS immunoreactivity. In conclusion, our data suggest the involvement of RAGE, at least partly, in mediating the effects of betaA(1-42) on CECs. In particular, the decrease of in vitro cell viability and functionality and nitrosative stress activation was inhibited by blocking betaA(1-42)-RAGE interaction.