AT2 receptor stimulation induces generation of ceramides in PC12W cells

FEBS Letters

Busche, Silke¹  Gallinat, Stefan¹  Krönke, Martin²  Schütze, Stefan²  Unger, Thomas¹ 

[1] Institute of Pharmacology, Christian-Albrechts-University of Kiel, Hospitalstr. 4, 24105 Kiel, Germany;Institute of Immunology, German Institute for High Blood Pressure Research, 69120 Heidelberg, Germany

关键词: Angiotensin II;    AT2 receptor;    Ceramide;    Apoptosis;    PC12W cell;   

DOI  :  10.1016/S0014-5793(98)01675-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 (10⁻⁸–5×10⁻⁶ M) increased ceramide levels by maximally 175% but did not affect sphingomyelin degradation. The ANG II 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.

【 授权许可】

Unknown