title: Involvement of acetylcholinesterase and protein kinase C in the protective effect of caffeine against β-amyloid-induced alterations in red blood cells.
abstract: It is well known the role of oxidative stress in the pathophysiology of Alzheimer's disease (AD) and of other neurodegenerative pathologies. We have previously documented that Amyloid beta peptide (1-42) (Abeta) dependent-oxidative modifications affect red blood cell (RBC) morphology and function. Experimental studies show that caffeine (CF) consumption is inversely correlated with AD. In this study, we investigated the role played by RBC in the protective mechanism elicited by CF against Abeta mediated toxicity. PS exposure levels by FACS analysis, as well as protein band 3 functionality analysis, indicated that CF at 100 μM protected against Abeta-mediated membrane alterations, which are known to occur in AD. Moreover, CF counteracts inhibition of ATP release from RBC by Abeta, restoring its ability to modulate vasodilation. Concurrently, analysis of protein kinase C (PKC) and caspase 3 activities, responsible for cytoskeleton alterations, revealed that unlike to caspase 3, PKCα activation induced by Abeta was fully abolished by CF through a mechanism involving Acetylcholinesterase (AChE), located on external face of RBC plasma membrane. These results provide support for the hypothesis concerning the protective role of CF in AD patients could include also a peripheral mechanism involving RBC.
authors.affiliation: Biochemistry and Clinical Biochemistry Institute, Catholic University, School of Medicine, L.go F. Vito n.1, 00168 Rome, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carelli-Alinovi
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ficarra
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Russo
authors.affiliation: Virology and Microbiology AOOR Papardo-Piemonte, V.le F. Stagno d'Alcontres, 98166 Messina, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Giunta
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Barreca
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galtieri
authors.affiliation: Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, V. S. Angelo, Loc. Folcara, Cassino, FR 03043, Italy. Electronic address: f.misiti@unicas.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Misiti
authors.affiliation: Department of Chemical Sciences, University of Messina, V.le F. Stagno d'Alcontres 31, 98166 Messina, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Tellone
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002110:Caffeine; D053148:Caspase 3 / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002110:Caffeine; D011493:Protein Kinase C; D000110:Acetylcholinesterase; D053148:Caspase 3
keywords: AChE; Alzheimer; Amyloid beta peptide; Caspase 3; Metabolism; PKC; Red blood cell