TY - JOUR
T1 - Anandamide induces apoptosis in human endothelial cells
T2 - Its regulation system and clinical implications
AU - Yamaji, Kazuyo
AU - Sarker, Krishna Pada
AU - Kawahara, Koichi
AU - Iino, Satoshi
AU - Yamakuchi, Munekazu
AU - Abeyama, Kazuhiro
AU - Hashiguchi, Teruto
AU - Maruyama, Ikuro
PY - 2003/5/1
Y1 - 2003/5/1
N2 - Anandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin Iβ-converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor I (VRI) antagonist, capsazepine, and was enhanced by a VRI agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VRI. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.
AB - Anandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin Iβ-converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor I (VRI) antagonist, capsazepine, and was enhanced by a VRI agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VRI. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.
KW - Anandamide
KW - Apoptosis
KW - Endothelial cell
KW - Endotoxin shock
KW - Vanilloid receptor I
UR - http://www.scopus.com/inward/record.url?scp=0037687434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037687434&partnerID=8YFLogxK
U2 - 10.1055/s-0037-1613475
DO - 10.1055/s-0037-1613475
M3 - Article
C2 - 12719786
AN - SCOPUS:0037687434
SN - 0340-6245
VL - 89
SP - 875
EP - 884
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 5
ER -