RESUMO
OBJECTIVE: To observe the relationship between murine double minute 2 (mdm2) expression and AngII and ceramide induced human umbilical endothelial cells apoptosis. METHOD: Human umbilical endothelial cells (ECs) were cultured in vitro and treated with angiotensin II alone or in combination with losartan (an inhibitor of AT1), PD123319 (an inhibitor of AT2) and FB1 (an inhibitor of ceramidase) respectively. ECs were also treated with different doses of C2-ceramide. The apoptosis of ECs was detected with Tunel, the mdm2 mRNA and protein expressions were measured with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: PD123319 and FB1 but not losartan inhibited AngII induced ECs apoptosis and down-regulated the AngII induced increased mdm2 expressions. C2-ceramide also induces ECs apoptosis and down-regulated mdm2 expressions at protein and mRNA levels in a dose-dependent manner. CONCLUSIONS: AngII binding with AT2 induces ECs apoptosis via ceramide. AngII and ceramide induce EC apoptosis by inhibiting mdm2.
