Estrogen prevents destabilization of endothelial nitric oxide synthase mRNA induced by tumor necrosis factor alpha through estrogen receptor mediated system.
17beta-estradiol up-regulates endothelial nitric oxide synthase (eNOS) expression in cultured endothelial cells. To clarify the role of mRNA stabilization in upregulation of eNOS expression, endothelial cells were incubated with actinomycin D as transcriptional inhibitor. Up to 10 hours incubation with 17beta-estradiol alone did not affect significantly the stability of eNOS mRNA. As tumor necrosis factor-alpha (TNF-alpha) is associated with the progression of atherosclerosis, we examined the effect of 17beta-estradiol on eNOS mRNA destabilization with TNF-alpha. After 10 hours co-incubation with TNF-alpha, relative intensity of eNOS mRNA decreased to 50% of the intensity at the start time of incubation, however, it remained significantly 1.6 times in the presence of 17beta-estradiol. This inhibitory effect of 17beta-estradiol was abolished by the treatment of estrogen receptor antagonist, ICI 182,780. This is the first finding that 17beta-estradiol stabilizes eNOS mRNA destabilized by TNF-alpha through estrogen receptor mediated mechanism.
Sumi
D
D
Department of Geriatrics, Nagoya University Graduate School of Medicine, Japan.
Hayashi
T
T
Jayachandran
M
M
Iguchi
A
A
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002417:Cattle; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004789:Enzyme Activation; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D000077267:Fulvestrant; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004965:Estrogen Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D000077267:Fulvestrant; D004958:Estradiol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III