Angiotensin II increases ceramide levels via the AT2 receptor in PC12W cells, suggesting a novel signal transduction pathway for AT2 receptor-mediated apoptosis.
The angiotensin AT2 receptor has been implicated in both regeneration and apoptosis. To further investigate the molecular mechanisms leading to AT2 receptor-induced programmed cell death in PC12W cells we studied the effects of angiotensin II (ANG II) on ceramide levels by HPTLC analysis. We could demonstrate that ANG II time- (1-10 h) and dose-dependently (10(-8)-5 X 10(-6) M) increased ceramide levels by maximally 175% but did not affect sphingomyelin degradation. The ANG 11 effects were mediated by AT2 receptors since they were completely abolished by co-incubation with the AT2 receptor antagonist, PD123177 (10(-5) M), but not by the AT1 receptor antagonist, losartan (10(-5) M). These data suggest a novel signal transduction pathway to the AT2 receptor leading to apoptosis in neuronal cells.
Gallinat et al. (1999) studied this question.
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