Cellular death in hippocampus in response to PI3K pathway inhibition and oxygen and glucose deprivation.
We investigated the importance of the phosphoinositide3-kinase (PI3K) pathway in CA1 and dentate gyrus (DG) areas of hippocampus by exposing organotypic cultures to LY294002, a PI3K inhibitor, or to oxygen and glucose deprivation (OGD) for up to 21 hours. LY294002 induced increased propidium iodide (PI) uptake and caspase 3/7 activity in both regions, with a faster onset in DG. In contrast, cultures exposed to 60 min of OGD showed a PI uptake only in the CA1 area, beginning 13 h after the insult and increasing until 21 h. We did not observe any significant changes in AKT phosphorylation and immunocontent in CA1 or DG areas of organotypic cultures exposed to OGD, suggesting that the phosphorylation of this protein at Ser-473 is unrelated to the cellular damage induced by ischemia. Our results suggest that the inhibition of the PI3K pathway does not mimic the cell death profile observed with an ischemic model.
Horn
Ana Paula
AP
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
Gerhardt
Daniéli
D
Geyer
Augusto Bencke
AB
Valentim
Lauren
L
Cimarosti
Helena
H
Tavares
Alexandre
A
Horn
Fabiana
F
Lenz
Guido
G
Salbego
Christianne
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D006624:Hippocampus / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology; D051058:Oncogene Protein v-akt; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015682:Retroviridae Proteins, Oncogenic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015682:Retroviridae Proteins, Oncogenic; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051058:Oncogene Protein v-akt; D020169:Caspases; D005947:Glucose