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Guanosine protects SH-SY5Y cells against β-amyloid-induced apoptosis

Pettifer, Kathleen M.1; Kleywegt, Sonya1 2; Bau, Christian J.1; Ramsbottom, James D.1 2 3; Vertes, Eva1; Ciccarelli, Renata2; Caciagli, Francesco2; Werstiuk, Eva S.1 CA; Rathbone, Michel P.1

Developmental Neuroscience

Apoptosis is implicated in the pathophysiology of Alzheimer's disease. Extracellular guanosine inhibits staurosporine-induced apoptosis in astrocytes. We examined whether guanosine protects SH-SY5Y human neuroblastoma cells against β-amyloid (βA)-induced apoptosis. Addition of βA (fragment 25-35, 5 μM for 24 h) to SH-SY5Y cells increased the number of apoptotic cells, as evaluated by oligonucleosome ELISA. Guanosine pre-treatment decreased βA-induced apoptosis (maximal effect after 24 h, 300 μM, p<0.05). The anti-apoptotic effect of guanosine was reduced by LY294002 (PI3K inhibitor) or PD98059 (MEK inhibitor) (p<0.05). Guanosine increased phosphorylation of Akt/PKB, and this was abolished by inhibiting PI3K or MEK, (p<0.001, 5 min). Thus, the protective effect of guanosine against βA-induced apoptosis of SH-SY5Y cells is mediated via activation of the PI3K/Akt/PKB and MAPK pathways.

1Department of Medicine, McMaster University, Health Sciences Centre, 4N71 1200 Main Street West, Hamilton, ON Canada, L8N 3Z5

2Department of Biomedical Sciences, School of Medicine, University of Chieti, Via dei Vestini 31, 66013 Chieti

3Department of Biomedical Sciences, Pharmacology, University of Trieste, Via Licio Giorgieri 7, 34127 Trieste, Italy

CACorresponding Author: wrstiuke@mcmaster.ca

Received 3 January 2004; accepted 3 February 2004

© 2004 Lippincott Williams & Wilkins, Inc.