Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells - Protective role in apoptosis

Hypoxia is a common environmental stress that influences signaling pathways and cell function. Several cell types, including neuroendocrine chromaffin cells, have evolved to sense oxygen levels and initiate specific adaptive responses to hypoxia. Here we report that under hypoxic conditions, rat phe ochromocytoma PC12 cells are resistant to apoptosis induced by serum withdr awal and chemotherapy treatment. This effect is also observed after treatme nt with deferoxamine, a compound that mimics many of the effects of hypoxia , The hypoxia-dependent protection from apoptosis correlates with activatio n of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is detecte d after 3-4 h of hypoxic or deferoxamine treatment and is sustained while h ypoxic conditions are maintained. Hypoxia-induced Akt activation can be pre vented by treatment with cycloheximide or actinomycin D, suggesting that de novo protein synthesis is required. Finally, inhibition of PI3K impairs bo th the protection against apoptosis and the activation of Akt in response t o hypoxia, suggesting a functional link between these two phenomena. Thus, reduced oxygen tension regulates apoptosis in PC12 cells through activation of the PI3K/Akt survival pathway.