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Cited by 386

The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.

Estrogen Induces the Akt-dependent Activation of Endothelial Nitric-oxide Synthase in Vascular Endothelial Cells

Open access
Hisamoto, Koji, Ohmichi, Masahide, Kurachi, Hirohisa, Hayakawa, Jun, Kanda, Yuki, Nishio, Yukihiro, Adachi, Kazushige, Tasaka, Keiichi, Miyoshi, Eiji, Fujiwara, Noriko, Taniguchi, Naoyuki, Murata, Yuji·2001·Journal of Biological Chemistry

Abstract

Although estrogen is known to activate endothelial nitric oxide synthase (eNOS) in the vascular endothelium, the molecular mechanism responsible for this effect remains to be elucidated. In studies of both human umbilical vein endothelial cells (HUVECs) and simian virus 40-transformed rat lung vascular endothelial cells (TRLECs), 17beta-estradiol (E2), but not 17alpha-E2, caused acute activation of eNOS that was unaffected by actinomycin D and was specifically blocked by the pure estrogen receptor antagonist ICI-182,780. Treatment of both TRLECs and HUVECs with 17beta-E2 stimulated the activation of Akt, and the PI3K inhibitor wortmannin blocked the 17beta-E2-induced activation of Akt. 17beta-E2-induced Akt activation was also inhibited by ICI-182,780, but not by actinomycin D. Either treatment with wortmannin or exogenous expression of a dominant negative Akt in TRLECs decreased the 17beta-E2-induced eNOS activation. Moreover, 17beta-E2-induced Akt activation actually enhances the phosphorylation of eNOS. 17beta-E2-induced Akt activation was dependent on both extracellular and intracellular Ca(2+). We further examined the 17beta-E2-induced Akt activity in Chinese hamster ovary (CHO) cells transiently transfected with cDNAs for estrogen receptor alpha (ERalpha) or estrogen receptor beta (ERbeta). 17beta-E2 stimulated the activation of Akt in CHO cells expressing ERalpha but not in CHO cells expressing ERbeta. Our findings suggest that 17beta-E2 induced eNOS activation through an Akt-dependent mechanism, which is mediated by ERalpha via a nongenomic mechanism.

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Crossref · 10.1074/jbc.m005036200

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Metadata

Authors
Hisamoto, K., Ohmichi, M., Kurachi, H., Hayakawa, J., Kanda, Y., Nishio, Y., Adachi, K., Tasaka, K., Miyoshi, E., Fujiwara, N., Taniguchi, N., & Murata, Y.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-02
Volume
276
Issue
5
Pages
3459-3467
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2127314614
Cited by
386
References
72
FWCI
19.50
Type
journal article
Language
en
Open access
hybrid

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Hisamoto, K., Ohmichi, M., Kurachi, H., Hayakawa, J., Kanda, Y., Nishio, Y., Adachi, K., Tasaka, K., Miyoshi, E., Fujiwara, N., Taniguchi, N., & Murata, Y. (2001). Estrogen Induces the Akt-dependent Activation of Endothelial Nitric-oxide Synthase in Vascular Endothelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m005036200

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