Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells.
Both neurons and glia succumb to programmed cell death (PCD) when deprived of growth factors at critical periods in development or following injury. Insulin-like growth factor-I (IGF-I) prevents apoptosis in neurons in vitro. To investigate whether IGF-I can protect Schwann cells (SC) from apoptosis, SC were harvested from postnatal day 3 rats and maintained in serum-containing media until confluency. When cells were switched to serum-free defined media (DM) for 12-72 h, they underwent PCD. Addition of insulin or IGF-I prevented apoptosis. Bisbenzamide staining revealed nuclear condensation and formation of apoptotic bodies in SC grown in DM alone, but SC grown in DM plus IGF-I had normal nuclear morphology. The phosphatidylinositol 3-kinase (PI 3-K) inhibitor LY294002 blocked IGF-I-mediated protection. Caspase-3 activity was rapidly activated upon serum withdrawal in SC, and the caspase inhibitor BAF blocked apoptosis. These results suggest that IGF-I rescues SC from apoptosis via PI 3-K signaling which is upstream from caspase activation.
Delaney
C L
CL
Department of Neurology, University of Michigan, 200 Zina Pitcher Place, 4414 Kresge III, Ann Arbor, Michigan 48109, USA.
Cheng
H L
HL
Feldman
E L
EL
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology*
D061945:Caspase Inhibitors; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D009025:Morpholines; D005576:Colforsin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one