Insulin-like growth factor-I (IGF-NGF withdrawal. The antiapoptotic effect of IGF-I I) is emerging as an important growth factor able to was completely blocked by LY294002, an inhibitor of modulate the programmed cell death (PCD) pathway mediated by the cysteine-dependent aspartate prote-PI 3-kinase
Insulin-like growth factor-I prevents caspase-mediated apoptosis in Schwann cells
β Scribed by Delaney, Catherine L. ;Cheng, Hsin-Lin ;Feldman, Eva L.
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 100 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0022-3034
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β¦ Synopsis
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.
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