[Homocysteine-induced apoptosis of endothelial cell and its antagonism by folic acid--the roles of caspase3, c-IAP1 and c-IAP2].
OBJECTIVE
The present study addresses the question how Hcy induces endothelial apoptosis and how folic acid antagonizes the proapoptotic effects of Hcy.


METHODS
Human umbilical vein endothelial cells (HUVEC) were treated with Hcy, with or without folic acid, for 24 hours. Cell apoptosis was evaluated by Annexin V staining and flow cytometery, as well as agarose gel analysis for genomic DNA ladder. The mRNA and protein levels of caspase3, c-IAP1, and c-IAP2 were analyzed by RT-PCR and Western blot, respectively.


RESULTS
Treatment with both low (0.3 mmol/L) and high (3.0 mmol/L) concentrations of Hcy induced HUVEC apoptosis, with higher apoptotic rate at the latter case. Hcy-induced HUVEC apoptosis was accompanied by an increased level of caspase3 expression and activation, together with decreased c-IAP2 level. Folic acid upregulated c-IAP2 expression while attenuating Hcy-induced apoptosis and caspase3 activation.


CONCLUSIONS
Hcy may induce HUVEC apoptosis via a pathway involving caspase3, which can be partially antagonized by folic acid, possibly through upregulated c-IAP2 expression.
Wang
Yufang
Y
College of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Zhou
Qiao
Q
Wang
Shuren
S
Zhang
Ji
J
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002469:Cell Separation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D014471:Umbilical Veins / Q000166:cytology
D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D006710:Homocysteine; D005492:Folic Acid; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases