Increased phospholipase D2 activity during hypoxia-induced death of PC12 cells: its possible anti-apoptotic role

During hypoxic incubation (1% O-2) of PC12 cells, the PLD activity was transiently increased within 12 h, followed by a gradual decrease. In the in vitro assay, the increased PLD activity was independent of GTP gammaS required for PLDI or of oleic acid for PLDOA, suggesting the activation of PLD2. The level of PLD2 protein showed no change up to 12 h but a gradual decrease after 24 h. pretreatment of cells with S. chromofuscus PLD resulted in inhibition of hypoxia-induced apoptotic cell death, in contrast, 1-butanol, but not 2-butanol, potentiated cell death. Moreover, the number of apoptotic cells significantly reduced in PC12 cells over-expressing PLD2. These results raise the possibility that PLD2 activation may play an anti-apoptotic role in hypoxia-induced cell death. NeuroReport 11:3647-3650 (C) 2000 Lippincott Williams & Wilkins.