Modifications of platelet from Alzheimer disease patients: a possible relation between membrane properties and NO metabolites.
Alzheimer disease (AD) is a chronic neurodegenerative disorder characterised by a progressive loss of memory and cognitive functions. The formation of nitric oxide (NO), by astrocytes, has been suggested to contribute to the neurodegnerative process. Some studies have described the participation of different isoforms of NOS in the progression of AD. The present work was conducted in order to investigate the role played by NO and peroxynitrite in platelets from AD patients, the possible correlation with Na(+)/K(+)-ATPase activity and the intracellular Ca(2+) in the same group of patients as well as the expression of NOS isoenzymes and nitrotyrosine as markers of NO synthesis and reactive protein nitration. NO production was significantly elevated in the platelets from AD patients compared to controls as well as l-arginine/NO-dependent ONOO(-). Membrane Na(+)/K(+)-ATPase activity was significantly decreased in patients than in controls while intracellular Ca(2+) concentration shows an opposite trend. Platelet from AD patients showed a significantly increased 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy compared with controls. Western blot analysis using anti-iNOS and eNOS monoclonal antibodies demonstrated that both isoforms were detectable in cell lysates as well as nitrotyrosine more pronounced in the cell lysates from AD patients than controls. In conclusion, the increased expression and activity of nitrergic system may produce platelet membrane alteration or vice versa. These modifications may contribute further to the neurodegenerative process in AD because the abnormal function of Alzheimer platelets play a very important role in the pathogenesis of the disease.
Vignini
Arianna
A
Institute of Biochemistry, School of Medicine, Università Politecnica delle Marche, Ancona, Italy. vignini2@libero.it <vignini2@libero.it>
Nanetti
Laura
L
Moroni
Cinzia
C
Tanase
Laura
L
Bartolini
Marco
M
Luzzi
Simona
S
Provinciali
Leandro
L
Mazzanti
Laura
L
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004161:Diphenylhexatriene / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D030421:Peroxynitrous Acid; D004161:Diphenylhexatriene; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium