33 306

Cited 0 times in

Phosphatidylinositol 3-kinase-mediated regulation of neuronal apoptosis and necrosis by insulin and IGF-I.

Ryu, BR; Ko, HW; Jou, I; Noh, JS; Gwag, BJ
Journal of neurobiology, 39(4):536-546, 1999
Journal Title
Journal of neurobiology
We examined effects of two insulin-like growth factors, insulin and insulin-like growth factor-I (IGF-I), against apoptosis, excitotoxicity, and free radical neurotoxicity in cortical cell cultures. Like IGF-I, insulin attenuated serum deprivation-induced neuronal apoptosis in a dose-dependent manner at 10-100 ng/mL. The anti-apoptosis effect of insulin against serum deprivation disappeared by addition of a broad protein kinase inhibitor, staurosporine, but not by calphostin C, a selective protein kinase C inhibitor. Addition of PD98059, a mitogen-activated protein kinase kinase (MAPKK) inhibitor, blocked insulin-induced activation of extracellular signal-regulated protein kinases (ERK1/2) without altering the neuroprotective effect of insulin. Cortical neurons underwent activation of phosphatidylinositol (PI) 3-kinase as early as 1 min after exposure to insulin. Inclusion of wortmannin or LY294002, selective inhibitors of PI 3-K, reversed the insulin effect against apoptosis. In contrast to the anti-apoptosis effect, neither insulin nor IGF-I protected excitotoxic neuronal necrosis following continuous exposure to 15 microM N-methyl-D-aspartate or 40 microM kainate for 24 h. Surprisingly, concurrent inclusion of 50 ng/mL insulin or IGF-I aggravated free radical-induced neuronal necrosis over 24 h following continuous exposure to 10 microM Fe2+ or 100 microM buthionine sulfoximine. Wortmannin or LY294002 also reversed this potentiation effect of insulin. These results suggest that insulin-like growth factors act as anti-apoptosis factor and pro-oxidant depending upon the activation of PI 3-kinase.
MeSH terms
Adenosine Triphosphate/pharmacologyAndrostadienes/pharmacologyAnimalsApoptosis/drug effectsApoptosis/physiology*Buthionine Sulfoximine/pharmacologyCalcium-Calmodulin-Dependent Protein Kinases/metabolismCells, CulturedChromones/pharmacologyEnzyme Activation/drug effectsEnzyme Activation/physiologyEnzyme Inhibitors/pharmacologyExcitatory Amino Acid Agonists/pharmacologyFlavonoids/pharmacologyHypoglycemic Agents/pharmacology*Insulin/pharmacology*Insulin Antagonists/pharmacologyInsulin-Like Growth Factor I/pharmacology*Iron/pharmacologyMiceMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases*Morpholines/pharmacologyN-Methylaspartate/pharmacologyNecrosisNeocortex/cytologyNeurons/cytology*Neurons/drug effectsNeurons/enzymologyNeuroprotective Agents/pharmacologyOxidative Stress/physiologyPhosphatidylinositol 3-Kinases/metabolism*Phosphorus Radioisotopes/diagnostic usePhosphorylationStaurosporine/pharmacology
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Psychiatry & Behavioural Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
주, 일로노, 재성곽, 병주
RIS (EndNote)
XLS (Excel)


해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.