The role of PI3/Akt pathway in the protective effect of insulin against corticosterone cell death induction in hippocampal cell culture.
Corticosterone induces neuroanatomical and neurochemical changes in the hippocampus that are associated with cognitive impairments. In the present study corticosterone induced cell death in primary hippocampal neurons cultured in Neurobasal + B27 medium. Insulin prevents neuronal cell death induced in a concentration dependent manner. The neuroprotective effect of insulin was reversed by LY294002, a phosphatidylinositol 3'-kinase (PI3 kinase) inhibitor, whereas the mitogen-activated protein kinase (MAPK) inhibitor PD98059, an upstream blocker of MAPK had no effect. Western blot analyses showed that insulin induced the activation of protein kinase B (Akt). These results suggest that insulin can prevent neuronal cell death induced by corticosterone in hippocampal neurons by modulating the activity of the PI3 kinase/Akt pathway.
Moosavi
Maryam
M
Department of Physiology, School of Medicine, Shahid Beheshti University, MC, Tehran, Iran.
Maghsoudi
Nader
N
Zahedi-Asl
Saleh
S
Naghdi
Nasser
N
Yousefpour
Mitra
M
Trounce
Ian Andrew
IA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D002867:Chromones; D003345:Corticosterone; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one