title: Involvement of the receptor for advanced glycation-end products (RAGE) in beta-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro.
abstract: 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.
authors.affiliation: Department of Biology, University of Padua, I-35121 Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baiguera
authors.forename: Lara
authors.initials: L
authors.lastname: Fioravanzo
authors.forename: Claudio
authors.initials: C
authors.lastname: Grandi
authors.forename: Rosa
authors.initials: R
authors.lastname: Di Liddo
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Parnigotto
authors.forename: Marcella
authors.initials: M
authors.lastname: Folin
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000098:blood supply*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008297:Male; D055806:Microvessels / Q000166:cytology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester