Protective effect of resveratrol against oxygen-glucose deprivation in organotypic hippocampal slice cultures: Involvement of PI3-K pathway.
Here we investigated the neuroprotective effect of resveratrol in an in vitro model of ischemia. We used organotypic hippocampal cultures exposed to oxygen-glucose deprivation (OGD). In OGD-vehicle exposed cultures, about 46% of the hippocampus was labeled with PI, indicating a robust percentage of cell death. When cultures were treated with resveratrol 10, 25 and 50 microM, the cell death was reduced to 22, 20 and 13% respectively. To elucidate a possible mechanism by which resveratrol exerts its neuroprotective effect, we investigated the phosphoinositide3-kinase (PI3-k) pathway using LY294002 (5 microM) and mitogen-activated protein kinase (MAPK) using PD98059 (20 microM). The resveratrol (50 microM) neuroprotection was prevented by LY294002 but was not by PD98059. Immunoblotting revealed that resveratrol 50 microM induced the phosphorylation/activation of Akt and extracellular signal-regulated kinase-1 and -2 (ERK1/2) and the phosphorylation/inactivation of glycogen synthase kinase-3beta (GSK-3beta). Our results suggest that PI3-k/Akt pathway are involved in the neuroprotective effect of resveratrol.
Zamin
Lauren L
LL
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, 90035-003, Porto Alegre, RS, Brazil.
Dillenburg-Pilla
Patrícia
P
Argenta-Comiran
Ricardo
R
Horn
Ana Paula
AP
Simão
Fabrício
F
Nassif
Melissa
M
Gerhardt
Daniéli
D
Frozza
Rudimar L
RL
Salbego
Christianne
C
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000502:physiology*; D002534:Hypoxia, Brain / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000502:physiology; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013267:Stilbenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005947:Glucose; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077185:Resveratrol; D013267:Stilbenes; C000605508:Gsk3b protein, rat