Expression and phosphorylation of protein kinase C isoforms in Abeta(1-42) activated T lymphocytes from Alzheimers disease.
The protein kinase C (PKC) family of enzymes is a regulator of transmembrane signal transduction. There is evidence demonstrating altered activity of some PKC isoforms (PKC-alpha, PKC-delta and PKC-zeta) in the neurons of brains of Alzheimers Disease (AD) sufferers, but little is known about their involvement in the intracellular machinery of amyloid beta protein-reactive T lymphocytes in AD. By applying a modified, split-well culture system, for Abeta(1-42) reactivity, we carried out flow cytometry analysis and biochemical investigations on the possible involvement of PKC-alpha, PKC-delta and PKC-zeta in the signalling system activated in Abeta-reactive T cells purified from peripheral blood mononucleate cells (PBMC) from healthy subjects and patients with AD. Flow cytometry analysis of Abeta(1-42) activated T lymphocytes in the majority of AD patients highlighted a distinct cellular cluster highly expressing phospho-PKC-delta (P-PKC-delta), while most full-blown AD patients highly expressed two distinct P-PKC-delta and phospho-PKC-zeta (P-PKC-zeta) bright sub-populations. The same investigation performed in freshly purified peripheral T lymphocytes, did not highlight any subpopulation, suggesting that the detection of P-PKC-delta and P-PKC-zeta bright subpopulations is specifically linked to Abeta(1-42) activated T lymphocytes. The data presented here, therefore, suggest possible novel hallmarks to discriminate between healthy elderly subjects and beginning or full-blown Alzheimers Disease patients.
Ciccocioppo
F
F
Cell Signalling Unit, Department of Biomorphology, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Lanuti
P
P
Marchisio
M
M
Gambi
F
F
Santavenere
E
E
Pierdomenico
L
L
Bascelli
A
A
Velluto
L
L
Gambi
D
D
Miscia
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008213:Lymphocyte Activation; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology*
D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D011493:Protein Kinase C