2-Methoxyestradiol, an endogenous metabolite of estrogen, enhances apoptosis and beta-galactosidase expression in vascular endothelial cells.
2-Methoxyestradiol (2ME) is an endogenous metabolite of estradiol (E2) and is known to inhibit tumor angiogenesis. In the present study, the direct effects of 2ME on the vascular endothelial cells were examined. 2ME enhanced apoptosis and beta-galactosidase expression in bovine vascular endothelial cells. A nitric oxide (NO) donor S-nitroso-N-acetyl penicillamin (SNAP) also enhanced beta-galactosidase expression, suggesting a possible role of NO in mediating the action of 2ME. 2ME increased the cellular content of nitric oxide synthase (NOS) and the production of NO. In addition, 2ME altered the membrane localization pattern of NOS. These suggest that the effects of 2ME on apoptosis and senescence of vascular endothelial cells were mediated, at least partly, by NOS and NO.
First Department of Medicine, Faculty of Medicine, University of Tokyo, Japan.
A
A
Tsukamoto
Y
Y
Kaneko
T
T
Yoshida
K
K
Han
M
M
Ichinose
S
S
Kimura
D000077584:2-Methoxyestradiol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003470:Culture Media; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism*
D003470:Culture Media; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D004958:Estradiol; D000077584:2-Methoxyestradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001616:beta-Galactosidase; D010396:Penicillamine