[Association between murine double minute 2 expression and AngII and ceramide induced endothelial cells apoptosis].
OBJECTIVE
To observe the relationship between murine double minute 2 (mdm2) expression and AngII and ceramide induced human umbilical endothelial cells apoptosis.


METHODS
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.
Yang
Li-xia
LX
Department of Cardiology, Kunming General Hospital of Chengdu Army, Kunming 650032, China.
Yang
Dong
D
Guo
Rui-wei
RW
Shen
Zhu-fu
ZF
Shi
Yan-kun
YK
Qi
Feng
F
Wang
Xian-mei
XM
D000804:Angiotensin II / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D007093:Imidazoles; C064769:N-acetylsphingosine; D011725:Pyridines; D012333:RNA, Messenger; D000804:Angiotensin II; C073402:PD 123319; D051736:Proto-Oncogene Proteins c-mdm2; D013110:Sphingosine