Guanosine protects SH-SY5Y cells against beta-amyloid-induced apoptosis.
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 beta-amyloid(betaA)-induced apoptosis. Addition of betaA (fragment 25-35, 5 microM for 24 h) to SH-SY5Y cells increased the number of apoptotic cells, as evaluated by oligonucleosome ELISA. Guanosine pre-treatment decreased betaA-induced apoptosis (maximal effect after 24 h, 300 microM, 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 betaA-induced apoptosis of SH-SY5Y cells is mediated via activation of the PI3K/Akt/PKB and MAPK pathways.
Pettifer
Kathleen M
KM
Department of Medicine, McMaster University, Health Sciences Centre, 4N71 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Kleywegt
Sonya
S
Bau
Christian J
CJ
Ramsbottom
James D
JD
Vertes
Eva
E
Ciccarelli
Renata
R
Caciagli
Francesco
F
Werstiuk
Eva S
ES
Rathbone
Michel P
MP
D064413:3-Phosphoinositide-Dependent Protein Kinases; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005419:Flavonoids / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013997:Time Factors
D016229:Amyloid beta-Peptides; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C074636:amyloid beta-protein (25-35); D006151:Guanosine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D064413:3-Phosphoinositide-Dependent Protein Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one