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 accessAbstract
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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Cited by
Gender, sex hormones, and vascular tone
Orshal, J. M., & Khalil, R. A. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00338.2003 · Cited by 650
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The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation
Napso, T., Yong, H. E. J., Lopez-Tello, J., & Sferruzzi-Perri, A. N. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01091 · Cited by 470
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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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