Cellular Biology |
From the Division of Cardiovascular Medicine and Molecular Cardiobiology, Boyer Center for Molecular Medicine (M.P.H., D.S., K.S.R., M.C., J.R.B.) and Department of Pharmacology (D.F., M.M.-R., W.C.S.), Yale University School of Medicine, New Haven, Conn.
Correspondence to Jeffrey R. Bender, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Ave, New Haven, CT 06536-0812. E-mail jeffrey.bender{at}yale.edu
| Abstract |
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Key Words: estrogen endothelial nitric oxide synthase Akt membrane receptor
| Introduction |
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The regulation of eNOS activity is multifaceted. This includes regulated palmitoylation and myristoylation, which are required for eNOS partitioning into membrane caveolae and consequent function.7 8 9 10 A variety of cofactors are required for enzymatic function, including Ca2+, calmodulin, and tetrahydrobiopterin.11 12 Recently, heat shock protein 90 (Hsp90) was demonstrated through its inducible association with eNOS to be a positive regulator of enzyme activity.13 We have previously shown that rapid activation by E2 of eNOS in human EC occurs in the absence of cytosolic Ca2+ increases. E2 and shear stress are two of the few agonists that can activate eNOS in this Ca2+ fluxindependent manner. However, the precise mechanism by which estrogen stimulates NO release is not known. As has been shown for other eNOS agonists, we have recently demonstrated that estrogen rapidly promotes an eNOS-Hsp90 association.14 Inhibition experiments with the Hsp90-specific agent geldanamycin confirmed that Hsp90 is required for E2-stimulated NO release. However, this has not elucidated the diminished requirement for Ca2+ in the setting of estrogen.
Recently, our laboratory15 and other studies16 17 demonstrated that the serine/threonine kinase Akt, a downstream effector of phosphatidylinositol-3-OH kinase (PI3-kinase), phosphorylates human eNOS on serine 1177 in response to varied stimuli, such as vascular endothelial growth factor (VEGF) and shear stress. This phosphorylation not only activates eNOS, but also seems to increase the efficiency of activation by Ca2+/calmodulin.18 Given the similarities between shear stressmediated and estrogen-mediated activation of eNOS, we evaluated the ability of estrogen to activate Akt in human ECs. We now show that E2 does indeed activate eNOS through a PI3-kinasedependent pathway. Because membrane impermeant estrogens trigger the same events, we discuss the activation pathway, from a putative, novel membrane estrogen receptor to distal components of the cascade, and its relevance in cardiovascular pathophysiology.
| Materials and Methods |
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30 mol
E2:molBSA) and ionomycin were purchased from
Sigma. E2 stocks were prepared in ethanol with
final ethanol concentrations
0.01%. LY294002 was purchased from
Calbiochem. ICI 182,780 was purchased from Zeneca Pharmaceuticals.
Stocks of LY294002 and ICI 182,780 were prepared in
Me2SO with final concentrations of
Me2SO
0.1%. Anti-eNOS (N30020) was from
Transduction Laboratories, and antiphosphorylated Akt
(pAKT), anti-Akt, and antiphosphorylated eNOS (peNOS)
were from New England Biolabs. All other reagents were purchased
from Sigma.
Cell Culture
The permanently established EA.hy926 endothelial
cell line19 was provided by CJS Edgell (University of
North Carolina). Cells were maintained in 10% FBS, which was DMEM
supplemented with 5 mmol/L hypoxanthine, 0.8 mmol/L
thymidine, and 20 µmol/L aminopterin. Human umbilical
vein endothelial cells (HUVECs) were isolated and maintained, as
previously described.6 Before E2
stimulation, cells were cultured in E2-free
medium, which was phenol-free DMEM with gelding horse serum (<1.0
pg/mL estradiol). After the initial E2
deprivation period, some cells were additionally
serum-starved for 4 to 16 hours for detection of
phosphorylated eNOS or phosphorylated
Akt in DMEM containing 0.1% fatty acidfree BSA.
NO Release Assays
NO-specific chemiluminescence, using potassium iodide and acetic
acid reflux, was used to determine the amount of
NO2- released from cell
monolayers, as previously described.15 Cells were switched
to E2-free medium for 48 hours, after when the
medium changed to HBSS supplemented with
CaCl2 (1.2 mmol/L),
MgSO4 (0.6 mmol/L), and L-arginine
(100 µmol/L) for 30 minutes before agonist stimulation. Cells
were stimulated with E2,
E2BSA, or ionomycin for 1 hour at 37°C, and
supernatants were collected for
NO2- analysis. To
address the requirements for ER engagement and the PI3-kinase pathway,
some cells were treated with ICI 182,780 or LY294002, respectively, for
1 hour before agonist stimulation. LY294002, when used in the 3- to
50-µmol/L concentration range, has been shown to be highly PI3-kinase
specific.20 21
Immunoprecipitation and Western Blotting
Cell monolayers were stimulated as described in the figure
legends. Phosphorylated Akt was detected in cell
lysates after 48-hour E2 deprivation
and overnight serum starvation. pAkt immunoblots were
stripped and blotted for total Akt. Phosphorylated eNOS
was detected after 48-hour E2
deprivation and 4-hour serum starvation from cell lysates
in solution containing (in mmol/L) Tris-HCl 20 (pH 7.4), EDTA 2.4,
Triton X-100 1%, sodium deoxycholate 1%, SDS 0.1%, NaCl 100, NaF 10,
Na3V04 1,
NaPiPO4 1, and protease inhibitor
cocktail (Roche). Lysates were incubated with anti-eNOS antibody
overnight at 4°C immunoprecipitated with protein A:protein G.
Immunoprecipitates were immunoblotted with anti-peNOS
(1:100) and anti-eNOS (1:2500) antibodies. Immunoblots were
probed with species-specific secondary antibodies coupled to
horseradish peroxidase and visualized by enhanced
chemiluminescence.
Adenoviral Infection of Cells
The recombinant adenoviruses expressing control
ß-galactosidase (ß-gal) and an Akt kinaseinactive mutant (AA-Akt)
were obtained from K. Walsh (St. Elizabeths Medical Center, Boston,
Mass) and were previously described.15 22 Monolayers were
incubated with recombinant adenovirus at a multiplicity of infection of
100. After infection, E2-free medium was added
for the cell recovery period followed by serum starvation in 0.1%
fatty acidfree BSA in phenol-free DMEM. Preliminary experiments with
the ß-gal encoding virus were used to established conditions optimal
for >95% cell culture transduction.
| Results |
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E2 Stimulates Downstream Targets of the PI3-Kinase
Pathway
One of the downstream targets of the PI3-kinase pathway is the
serine/threonine kinase Akt/PKB. Known Akt substrates include eNOS as
well as several proteins involved in cell survival and glucose
metabolism.23 24 Because
E2-stimulated NO release is largely
PI3-kinasedependent, we addressed whether E2
treatment could also result in Akt activation. To test this, both
EA.hy926 and HUVEC cell lysates were prepared from
E2-stimulated or vehicle controlstimulated
cells. When using an antibody directed at the serine
473phosphorylated, activated form of Akt,
phosphorylation was detected within 5 minutes of
E2 treatment in both cell types and persisted for
at least 30 minutes (Figure 2
).
Dose-response experiments demonstrated induced
endothelial Akt activation with as little as 100 pg/mL
E2 (data not shown). These results and the
PI3-kinase inhibition data demonstrate that E2
can activate endothelial PI3-kinase, resulting
in the presumed translocation of Akt to the plasma membrane, where it
is activated by phosphorylation.
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The kinetics of E2-stimulated EC Akt
phosphorylation correlate with the rapid, nongenomic
activation of eNOS we have reported previously.6 14 eNOS
has been classically described as a
Ca2+/calmodulin-dependent
enzyme.12 However, we have demonstrated that the
E2-induced increase in EC-NO release occurs
without a cytosolic Ca2+ increase and does not
alter the amount of eNOS-associated
calmodulin.14 Recently, our
laboratories15 and other studies17 have
demonstrated that the phosphorylation of human eNOS
serine 1177 (serine 1179 in bovine eNOS) by Akt lowers the apparent
Ca2+/calmodulin requirements of the
enzyme. Thus, using an antibody specific for this Akt substrate,
phosphorylated eNOS site, Western blot analyses
were performed to determine whether E2
stimulation does, in fact, result in EC eNOS
phosphorylation. ECs were
E2-deprived and serum-starved before stimulation
with E2 or vehicle control. As shown in Figure 3A
, specifically
phosphorylated eNOS was easily detected within 5
minutes of E2 exposure.
Phosphorylated eNOS persists for at least 30 minutes
and is phosphorylated to the same extent as
endothelial cells treated with VEGF (Figure 3B
),
a known inducer of bovine eNOS
phosphorylation.15 Thus, the kinetics of
E2-stimulated Akt
phosphorylation, eNOS phosphorylation,
and EC-NO release are all consistent.
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Dominant-Negative Form of Akt Blocks E2-Stimulated
NO Release
To directly establish that the E2-triggered
signal transduction pathway resulting in NO release proceeds through
Akt, EA.hy926 cells were transduced with adenoviral vectors encoding an
AA-Akt or control ß-gal. AA-Akt has been shown to block
VEGF-stimulated NO release.15 Additionally,
kinase-inactive Akt is unable to phosphorylate eNOS in
response to shear stress and thus is unable to enhance NO release in
that setting.17 Cells were infected with the adenovirus
for 2 hours, incubated for 24 hours in
E2-deficient serum, and kept serum-free for an
additional 24 hours. As has been described with other ECs, the
transduction efficiency was very high, with positive ß-gal staining
in >95% of ß-galtransduced cells (data not shown). Cells infected
with control (ß-gal) exhibited a 2.25-fold increase in
E2-stimulated NO release similar to the 2.5-fold
induction seen in noninfected cells (Figure 4
), whereas AA-Akt expression largely
abrogated E2-stimulated NO production.
This demonstrates that functionally active Akt is required for
E2-stimulated NO release.
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Cell-Impermeant E2 Activates the
PI3-Kinase/Akt Pathway
The existence of cell-surface steroid hormone receptors has been
debated. Recently, membrane progesterone receptors have been detected
and shown to be physiologically
active.25 In addition, overexpression of ER
and ß in
Chinese hamster ovary cells results in the detection of a few surface
ERs that can respond to E2.26
E2 conjugated to BSA is membrane-impermeant and
has been used to detect surface binding sites for
E2.14 27 28 We have described an
apparent EC-membrane ER capable of rapidly inducing NO release and
activating mitogen-activated protein (MAP) kinase (ERK
1/2).29 E2BSA was thus used to
determine whether the PI3-kinase/Akt pathway can be activated
by engagement of a surface ER. Cell monolayers were stimulated with
E2BSA or vehicle in the presence of excess fatty
acidfree BSA. Figure 5
demonstrates
that E2BSA does trigger Akt
phosphorylation. Similar to that seen with
cell-permeant E2,
E2BSA-stimulated Akt
phosphorylation occurs within 5 minutes (Figure 5
) and persists for at least 30 minutes (data not shown).
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To again determine whether this Akt activation is required for NO
release, ECs were AA-Akttransduced or ß-galtransduced with the
respective adenovirus before stimulation with
E2BSA or vehicle control. Figure 6
demonstrates that cells overexpressing
kinase-inactive Akt were unable to generate any
E2-stimulated NO release, whereas control
ß-galtransduced cells maintained an excellent response to
E2BSA. This indicates that
E2 can stimulate an increase in NO via a surface
receptor that signals through the PI3-kinase/Akt pathway. As expected,
E2BSA triggered the critical, Akt-induced
phosphorylation on eNOS serine 1177 within 5 minutes
(Figure 7
). Thus, all the activation
events induced by free E2 can be reproduced by
engagement of a surface ER.
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| Discussion |
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eNOS is a Ca2+ and calmodulin-dependent enzyme, and its regulated activation by agonists such as histamine and acetylcholine seems to require a stimulated rise in intracellular Ca2+.31 However, recent evidence supports that several stimuli, including fluid shear stress,32 insulin,33 and estrogen,6 can activate eNOS and augment NO release in the absence of identifiable Ca2+ fluxes and in the setting of Ca2+ chelation. This apparent paradox has been difficult to reconcile and, in the context of estrogen, has been debated.34 Recently, our laboratories15 and other studies16 17 have shown that Akt phosphorylates human eNOS on a critical serine 1177 (1179 in bovine eNOS). Altering the charge on this residue, either through Akt-induced phosphorylation or by mutagenesis-based substitution with aspartate, is associated with an increase in NO production and enzyme activation at much lower Ca2+ and calmodulin concentrations.15 16 17 That is, Akt-induced eNOS phosphorylation greatly increases the activity of eNOS at resting Ca2+ concentrations. This is based, in part, on a faster rate of electron flux through the eNOS reductase domain and a reduced calmodulin dissociation from eNOS when Ca2+ levels are low.18 Phosphorylation may confer a conformational alteration on the interaction of calmodulin with the 45 amino acid autoinhibitory flavin mononucleotide insert domain or in the carboxy tail, thereby effecting disinhibition. Our results clearly demonstrate that E2 stimulates human endothelial Akt activation and eNOS phosphorylation. The findings that PI3-kinasedependent Akt activation is not Ca2+-dependent and that this specific serine 1177 phosphorylation enhances eNOS Ca2+ sensitivity are consistent with our previous data that estrogen-stimulated endothelial NO release does not require a rise in free intracellular Ca2+ and provide the first mechanistic explanation of how this may occur.
The signaling cascade leading to PI3-kinase/Akt activation by E2 is presently unknown. There are many examples of growth factors stimulating hormone-independent estrogen receptormediated events through phosphorylation of the critical ER transactivation function domain-1.35 36 However, details of the converse have not been defined. That is, the PI3-kinase/Akt activation by estrogen demonstrated here, and inhibited by conventional ER antagonists, depicts rapid growth factor receptortype responses induced by a steroid hormone. In the mouse uterus, estrogen has been shown to trigger the tyrosine phosphorylation of insulin-like growth factor receptor-1 (IGF-1R), as well as tyrosine phosphorylation of the docking substrate IRS-1 and consequent IGF-1R/IRS-1/PI3-kinase p85 complex formation.37 38 This induced recruitment of the regulatory unit of PI3-kinase is sufficient to initiate enzyme activation. Much of the estrogen-induced p85-IGF-1R association was absent in IGF-1deficient mice, suggesting that a majority of this pathway activation is a consequence of E2-stimulated IGF-1 synthesis. However, residual induced p85-IGF-1R complexes remained in the absence of IGF-1. Estrogen-induced recruitment of p85 to tyrosine kinase growth factor receptors could be responsible for the signaling events described in this study.
Other potential cascades should be considered on the basis of several analogies between fluid shear stressstimulated and estrogen-stimulated eNOS activation, including the induction of relative Ca2+ independence. Shear stress activates Akt in a PI3-kinasedependent fashion, and consequent NO production is inhibited by the PI3-kinase inhibitor wortmannin.17 Shear stress induces a clustering of the VEGF receptor Flk-1 and its rapid tyrosine phosphorylation and association with the adapter protein Shc, which can result in Ras activation and subsequent MAP kinase induction through the assembly of Shc/Grb2/SOS complexes.39 Our laboratories14 and other studies40 have demonstrated a rapid MAP kinase activation induced by E2 in ECs. In addition to its role in the MAP kinase pathway, GTP-bound Ras can also activate PI3-kinase.41 This is another potential signaling pathway by which E2 could trigger EC-NO release.
We recently demonstrated that Hsp90 is rapidly recruited to eNOS on endothelial treatment with E2.14 Geldanamycin, which binds to the ATP-binding site of Hsp90 and inhibits its function, abrogates E2-stimulated EC-NO release. The relationship between Hsp90 recruitment and Akt activation, both triggered by E2 and required for stimulated eNOS activation, remains unclear. Herbimycin A, in the same pharmacological class as geldanamycin, does not block shear stressinduced Akt activation. Considering the analogy to estrogen responses, this suggests either that functional Hsp90-eNOS association is a critical downstream mediator of eNOS activation or that the pathways by which Akt and Hsp90 regulate eNOS activity, as induced by estrogen, are both required but independent. We are presently investigating the interplay between estrogen-induced Hsp90-eNOS association and modulation of eNOS by Akt.
Finally, one must consider the most proximal signal transduction
event in response to E2: that of ER engagement.
The events described occur rapidly, are inhibited by conventional ER
antagonists, and are consistent with rapid
transmembrane signaling. Our results demonstrate for the first time
that PI3-kinase and Akt activation can be triggered with the cell
impermeant E2BSA conjugate. We have used this
conjugate extensively, including after charcoal extraction of any free
E2, and determined E2BSA
binding sites on human EC membranes that are competitively blocked by
conventional ER antagonists and free
E2.29 As opposed to uterine and
breast cells, in which estrogen has been shown to activate
PI3-kinase,38 42 EA.hy926 ECs, used in these experiments,
do not express the traditional 66 kDa ER
(or ERß) nor are they
able to undergo the normal E2-stimulated,
ER-dependent gene transactivation (Reference 2929 and unpublished data,
July 2000). However, they do express a 45-kDa protein,
immunoreactive with an antiC-terminal ER
antibody, which seems to
correlate with intact rapid signaling responses.29
Experiments to identify this molecule are presently underway.
In summary, we have found that the mechanism by which estrogen stimulates endothelial NO production involves a rapid, PI3-kinasedependent activation of Akt and consequent serine phosphorylation of eNOS. These activation events occur after engagement of membrane receptors for estrogen. This explains the emerging paradigm relating rapid, estrogen-stimulated endothelial signaling, enhanced eNOS sensitivity to cytosolic Ca2+, and unconventional estrogen receptors. Additional definition of these receptors and the proximal signaling events leading to Akt activation will provide opportunities for specialized therapeutic interventions in cardiovascular disease.
| Acknowledgments |
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Received August 7, 2000; revision received September 1, 2000; accepted September 6, 2000.
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J. P. Stice, J. P. Eiserich, and A. A. Knowlton Role of Aging Versus the Loss of Estrogens in the Reduction in Vascular Function in Female Rats Endocrinology, January 1, 2009; 150(1): 212 - 219. [Abstract] [Full Text] [PDF] |
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Md. S. Bhuiyan, N. Shioda, M. Shibuya, Y. Iwabuchi, and K. Fukunaga Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats Hypertension, January 1, 2009; 53(1): 57 - 63. [Abstract] [Full Text] [PDF] |
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H.-N. Kung, M.-J. Yang, C.-F. Chang, Y.-P. Chau, and K.-S. Lu In vitro and in vivo wound healing-promoting activities of {beta}-lapachone Am J Physiol Cell Physiol, October 1, 2008; 295(4): C931 - C943. [Abstract] [Full Text] [PDF] |
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R. Matyal Newly Appreciated Pathophysiology of Ischemic Heart Disease in Women Mandates Changes in Perioperative Management: A Core Review Anesth. Analg., July 1, 2008; 107(1): 37 - 50. [Abstract] [Full Text] [PDF] |
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J.-Z. Sheng, F. Arshad, J. E. Braun, and A. P. Braun Estrogen and the Ca2+-mobilizing agonist ATP evoke acute NO synthesis via distinct pathways in an individual human vascular endothelium-derived cell Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1531 - C1541. [Abstract] [Full Text] [PDF] |
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E. Grossini, C. Molinari, D. A. S. G. Mary, F. Uberti, P. P. Caimmi, N. Surico, and G. Vacca Intracoronary Genistein Acutely Increases Coronary Blood Flow in Anesthetized Pigs through {beta}-Adrenergic Mediated Nitric Oxide Release and Estrogenic Receptors Endocrinology, May 1, 2008; 149(5): 2678 - 2687. [Abstract] [Full Text] [PDF] |
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P. D. Patel and R. R. Arora Review: Endothelial dysfunction: A potential tool in gender related cardiovascular disease Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 89 - 100. [Abstract] [PDF] |
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C. Grossmann, R. Freudinger, S. Mildenberger, B. Husse, and M. Gekle EF Domains Are Sufficient for Nongenomic Mineralocorticoid Receptor Actions J. Biol. Chem., March 14, 2008; 283(11): 7109 - 7116. [Abstract] [Full Text] [PDF] |
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E. Chang, M. E. O'Donnell, and A. I. Barakat Shear stress and 17{beta}-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels Am J Physiol Cell Physiol, January 1, 2008; 294(1): C363 - C371. [Abstract] [Full Text] [PDF] |
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Md. S. Bhuiyan, N. Shioda, and K. Fukunaga Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1606 - E1614. [Abstract] [Full Text] [PDF] |
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A. Zoubeidi, A. Zardan, E. Beraldi, L. Fazli, R. Sowery, P. Rennie, C. Nelson, and M. Gleave Cooperative Interactions between Androgen Receptor (AR) and Heat-Shock Protein 27 Facilitate AR Transcriptional Activity Cancer Res., November 1, 2007; 67(21): 10455 - 10465. [Abstract] [Full Text] [PDF] |
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M. Liu, N. Yanagihara, Y. Toyohira, M. Tsutsui, S. Ueno, and Y. Shinohara Dual Effects of Daidzein, a Soy Isoflavone, on Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells Endocrinology, November 1, 2007; 148(11): 5348 - 5354. [Abstract] [Full Text] [PDF] |
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L. Li, K. Hisamoto, K. H. Kim, M. P. Haynes, P. M. Bauer, A. Sanjay, M. Collinge, R. Baron, W. C. Sessa, and J. R. Bender Variant estrogen receptor c-Src molecular interdependence and c-Src structural requirements for endothelial NO synthase activation PNAS, October 16, 2007; 104(42): 16468 - 16473. [Abstract] [Full Text] [PDF] |
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D. Sun, C. Yan, A. Jacobson, H. Jiang, M. A. Carroll, and A. Huang Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ER{alpha} knockout mice: role of aromatase Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1239 - R1246. [Abstract] [Full Text] [PDF] |
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E. Hirsch, C. Costa, and E. Ciraolo Phosphoinositide 3-kinases as a common platform for multi-hormone signaling J. Endocrinol., August 1, 2007; 194(2): 243 - 256. [Abstract] [Full Text] [PDF] |
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G. E. Mann, D. J. Rowlands, F. Y.L. Li, P. de Winter, and R. C.M. Siow Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression Cardiovasc Res, July 15, 2007; 75(2): 261 - 274. [Abstract] [Full Text] [PDF] |
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D. Liu, H. Si, K. A. Reynolds, W. Zhen, Z. Jia, and J. S. Dillon Dehydroepiandrosterone Protects Vascular Endothelial Cells against Apoptosis through a G{alpha}i Protein-Dependent Activation of Phosphatidylinositol 3-Kinase/Akt and Regulation of Antiapoptotic Bcl-2 Expression Endocrinology, July 1, 2007; 148(7): 3068 - 3076. [Abstract] [Full Text] [PDF] |
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G. Han, H. Ma, R. Chintala, K. Miyake, D. J. R. Fulton, S. A. Barman, and R. E. White Nongenomic, endothelium-independent effects of estrogen on human coronary smooth muscle are mediated by type I (neuronal) NOS and PI3-kinase-Akt signaling Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H314 - H321. [Abstract] [Full Text] [PDF] |
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A. Zheng, A. Kallio, and P. Harkonen Tamoxifen-Induced Rapid Death of MCF-7 Breast Cancer Cells Is Mediated via Extracellularly Signal-Regulated Kinase Signaling and Can Be Abrogated by Estrogen Endocrinology, June 1, 2007; 148(6): 2764 - 2777. [Abstract] [Full Text] [PDF] |
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A.-M. Jaubert, N. Mehebik-Mojaat, D. Lacasa, D. Sabourault, Y. Giudicelli, and C. Ribiere Nongenomic Estrogen Effects on Nitric Oxide Synthase Activity in Rat Adipocytes Endocrinology, May 1, 2007; 148(5): 2444 - 2452. [Abstract] [Full Text] [PDF] |
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J. G. Greger, N. Fursov, N. Cooch, S. McLarney, L. P. Freedman, D. P. Edwards, and B. J. Cheskis Phosphorylation of MNAR Promotes Estrogen Activation of Phosphatidylinositol 3-Kinase Mol. Cell. Biol., March 1, 2007; 27(5): 1904 - 1913. [Abstract] [Full Text] [PDF] |
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N. Vasudevan and D. W. Pfaff Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles Endocr. Rev., February 1, 2007; 28(1): 1 - 19. [Abstract] [Full Text] [PDF] |
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C. Pinna, C. Bolego, P. Sanvito, V. Pelosi, R. Baetta, A. Corsini, R. M. Gaion, and A. Cignarella Raloxifene Elicits Combined Rapid Vasorelaxation and Long-Term Anti-Inflammatory Actions in Rat Aorta J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1444 - 1451. [Abstract] [Full Text] [PDF] |
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K. Moriarty, K. H. Kim, and J. R. Bender Estrogen Receptor-Mediated Rapid Signaling Endocrinology, December 1, 2006; 147(12): 5557 - 5563. [Abstract] [Full Text] [PDF] |
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M. A. Sovershaev, E. M. Egorina, T. V. Andreasen, A. K. Jonassen, and K. Ytrehus Preconditioning by 17beta-estradiol in isolated rat heart depends on PI3-K/PKB pathway, PKC, and ROS Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1554 - H1562. [Abstract] [Full Text] [PDF] |
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V. P. Cokic, B. B. Beleslin-Cokic, M. Tomic, S. S. Stojilkovic, C. T. Noguchi, and A. N. Schechter Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells Blood, July 1, 2006; 108(1): 184 - 191. [Abstract] [Full Text] [PDF] |
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Y. Seval, H. Cakmak, U. A. Kayisli, and A. Arici Estrogen-Mediated Regulation of p38 Mitogen-Activated Protein Kinase in Human Endometrium J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2349 - 2357. [Abstract] [Full Text] [PDF] |
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J. A. Sullivan, M. A. Grummer, F.-X. Yi, and I. M. Bird Pregnancy-Enhanced Endothelial Nitric Oxide Synthase (eNOS) Activation in Uterine Artery Endothelial Cells Shows Altered Sensitivity to Ca2+, U0126, and Wortmannin But Not LY294002--Evidence that Pregnancy Adaptation of eNOS Activation Occurs at Multiple Levels of Cell Signaling Endocrinology, May 1, 2006; 147(5): 2442 - 2457. [Abstract] [Full Text] [PDF] |
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A. Toyofuku, T. Hara, T. Taguchi, Y. Katsura, K. Ohama, and Y. Kudo Cyclic and characteristic expression of phosphorylated Akt in human endometrium and decidual cells in vivo and in vitro Hum. Reprod., May 1, 2006; 21(5): 1122 - 1128. [Abstract] [Full Text] [PDF] |
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M. Almeida, L. Han, C. A. O'Brien, S. Kousteni, and S. C. Manolagas Classical Genotropic Versus Kinase-Initiated Regulation of Gene Transcription by the Estrogen Receptor {alpha} Endocrinology, April 1, 2006; 147(4): 1986 - 1996. [Abstract] [Full Text] [PDF] |
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C. Mineo and P. W. Shaul Circulating cardiovascular disease risk factors and signaling in endothelial cell caveolae Cardiovasc Res, April 1, 2006; 70(1): 31 - 41. [Abstract] [Full Text] [PDF] |
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W. R. Harrington, S. H. Kim, C. C. Funk, Z. Madak-Erdogan, R. Schiff, J. A. Katzenellenbogen, and B. S. Katzenellenbogen Estrogen Dendrimer Conjugates that Preferentially Activate Extranuclear, Nongenomic Versus Genomic Pathways of Estrogen Action Mol. Endocrinol., March 1, 2006; 20(3): 491 - 502. [Abstract] [Full Text] [PDF] |
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Z. Yang and X.-F. Ming Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin. Med. Res., March 1, 2006; 4(1): 53 - 65. [Abstract] [Full Text] [PDF] |
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L. C. Anderson, D. J. Martin, D. L. Phillips, K. J. Killpack, S. E. Bone, and R. Rahimian The influence of gender on parasympathetic vasodilatation in the submandibular gland of the rat Exp Physiol, March 1, 2006; 91(2): 435 - 444. [Abstract] [Full Text] [PDF] |
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D. Cevik, O. Unay, F. Durmusoglu, T. Yurdun, and A S. Bilsel Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA Vascular Medicine, February 1, 2006; 11(1): 7 - 12. [Abstract] [PDF] |
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V. L. Ballard and J. M. Edelberg Harnessing Hormonal Signaling for Cardioprotection Sci. Aging Knowl. Environ., December 21, 2005; 2005(51): re6 - re6. [Abstract] [Full Text] [PDF] |
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J. S. Lewis, K. Meeke, C. Osipo, E. A. Ross, N. Kidawi, T. Li, E. Bell, N. S. Chandel, and V. C. Jordan Intrinsic Mechanism of Estradiol-Induced Apoptosis in Breast Cancer Cells Resistant to Estrogen Deprivation J Natl Cancer Inst, December 7, 2005; 97(23): 1746 - 1759. [Abstract] [Full Text] [PDF] |
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C. R. White, M. W. Hamade, K. Siami, M. M. Chang, A. Mangalwadi, J. A. Frangos, and W. J. Pearce Maturation enhances fluid shear-induced activation of eNOS in perfused ovine carotid arteries Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2220 - H2227. [Abstract] [Full Text] [PDF] |
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A. Uruno, A. Sugawara, H. Kanatsuka, H. Kagechika, A. Saito, K. Sato, M. Kudo, K. Takeuchi, and S. Ito Upregulation of Nitric Oxide Production in Vascular Endothelial Cells by All-trans Retinoic Acid Through the Phosphoinositide 3-Kinase/Akt Pathway Circulation, August 2, 2005; 112(5): 727 - 736. [Abstract] [Full Text] [PDF] |
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C. Grossmann, A. Benesic, A. W. Krug, R. Freudinger, S. Mildenberger, B. Gassner, and M. Gekle Human Mineralocorticoid Receptor Expression Renders Cells Responsive for Nongenotropic Aldosterone Actions Mol. Endocrinol., July 1, 2005; 19(7): 1697 - 1710. [Abstract] [Full Text] [PDF] |
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E. Schulz, E. Anter, M.-H. Zou, and J. F. Keaney Jr Estradiol-Mediated Endothelial Nitric Oxide Synthase Association With Heat Shock Protein 90 Requires Adenosine Monophosphate-Dependent Protein Kinase Circulation, June 28, 2005; 111(25): 3473 - 3480. [Abstract] [Full Text] [PDF] |
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K. H. Kim and J. R. Bender Rapid, Estrogen Receptor-Mediated Signaling: Why Is the Endothelium So Special? Sci. Signal., June 14, 2005; 2005(288): pe28 - pe28. [Abstract] [Full Text] [PDF] |
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P. L. Huang Unraveling the Links Between Diabetes, Obesity, and Cardiovascular Disease Circ. Res., June 10, 2005; 96(11): 1129 - 1131. [Full Text] [PDF] |
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D. Rai, A. Frolova, J. Frasor, A. E. Carpenter, and B. S. Katzenellenbogen Distinctive Actions of Membrane-Targeted Versus Nuclear Localized Estrogen Receptors in Breast Cancer Cells Mol. Endocrinol., June 1, 2005; 19(6): 1606 - 1617. [Abstract] [Full Text] [PDF] |
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E. Anter, K. Chen, O. M. Shapira, R. H. Karas, and J. F. Keaney Jr p38 Mitogen-Activated Protein Kinase Activates eNOS in Endothelial Cells by an Estrogen Receptor {alpha}-Dependent Pathway in Response to Black Tea Polyphenols Circ. Res., May 27, 2005; 96(10): 1072 - 1078. [Abstract] [Full Text] [PDF] |
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X. Guo, M. Razandi, A. Pedram, G. Kassab, and E. R. Levin Estrogen Induces Vascular Wall Dilation: MEDIATION THROUGH KINASE SIGNALING TO NITRIC OXIDE AND ESTROGEN RECEPTORS {alpha} AND {beta} J. Biol. Chem., May 20, 2005; 280(20): 19704 - 19710. [Abstract] [Full Text] [PDF] |
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G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [Abstract] [Full Text] [PDF] |
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C. M. Klinge, K. A. Blankenship, K. E. Risinger, S. Bhatnagar, E. L. Noisin, W. K. Sumanasekera, L. Zhao, D. M. Brey, and R. S. Keynton Resveratrol and Estradiol Rapidly Activate MAPK Signaling through Estrogen Receptors {alpha} and {beta} in Endothelial Cells J. Biol. Chem., March 4, 2005; 280(9): 7460 - 7468. [Abstract] [Full Text] [PDF] |
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C. Dimitropoulou, R. E. White, D. R. Ownby, and J. D. Catravas Estrogen Reduces Carbachol-Induced Constriction of Asthmatic Airways by Stimulating Large-Conductance Voltage and Calcium-Dependent Potassium Channels Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 239 - 247. [Abstract] [Full Text] [PDF] |
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H. J. Garban, D. C. Marquez-Garban, R. J. Pietras, and L. J. Ignarro Rapid nitric oxide-mediated S-nitrosylation of estrogen receptor: Regulation of estrogen-dependent gene transcription PNAS, February 15, 2005; 102(7): 2632 - 2636. [Abstract] [Full Text] [PDF] |
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K. L. Chambliss, L. Simon, I. S. Yuhanna, C. Mineo, and P. W. Shaul Dissecting the Basis of Nongenomic Activation of Endothelial Nitric Oxide Synthase by Estradiol: Role of ER{alpha} Domains with Known Nuclear Functions Mol. Endocrinol., February 1, 2005; 19(2): 277 - 289. [Abstract] [Full Text] [PDF] |
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C. Stirone, A. Boroujerdi, S. P. Duckles, and D. N. Krause Estrogen Receptor Activation of Phosphoinositide-3 Kinase, Akt, and Nitric Oxide Signaling in Cerebral Blood Vessels: Rapid and Long-Term Effects Mol. Pharmacol., January 1, 2005; 67(1): 105 - 113. [Abstract] [Full Text] [PDF] |
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Q. Lu, D. C. Pallas, H. K. Surks, W. E. Baur, M. E. Mendelsohn, and R. H. Karas Striatin assembles a membrane signaling complex necessary for rapid, nongenomic activation of endothelial NO synthase by estrogen receptor {alpha} PNAS, December 7, 2004; 101(49): 17126 - 17131. [Abstract] [Full Text] [PDF] |
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K. Morimoto, Y. Kurahashi, K. Shintani-Ishida, N. Kawamura, M. Miyashita, M. Uji, N. Tan, and K.-i. Yoshida Estrogen replacement suppresses stress-induced cardiovascular responses in ovariectomized rats Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H1950 - H1956. [Abstract] [Full Text] [PDF] |
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A. F. Kernohan, A. Spiers, N. Sattar, C. Hillier, S. J Cleland, M. Small, M.-A. Lumsden, J. M. Connell, and J. R Petrie Effects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes Diabetes and Vascular Disease Research, October 1, 2004; 1(2): 82 - 88. [Abstract] [PDF] |
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R. D. Patten, I. Pourati, M. J. Aronovitz, J. Baur, F. Celestin, X. Chen, A. Michael, S. Haq, S. Nuedling, C. Grohe, et al. 17{beta}-Estradiol Reduces Cardiomyocyte Apoptosis In Vivo and In Vitro via Activation of Phospho-Inositide-3 Kinase/Akt Signaling Circ. Res., October 1, 2004; 95(7): 692 - 699. [Abstract] [Full Text] [PDF] |
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H. Aramoto, J. W. Breslin, P. J. Pappas, R. W. Hobson II, and W. N. Duran Vascular endothelial growth factor stimulates differential signaling pathways in in vivo microcirculation Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1590 - H1598. [Abstract] [Full Text] [PDF] |
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K. L. Hamilton, F.N. Mbai, S. Gupta, and A.A. Knowlton Estrogen, Heat Shock Proteins, and NF{kappa}B in Human Vascular Endothelium Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1628 - 1633. [Abstract] [Full Text] [PDF] |
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O. Guzeloglu Kayisli, U. A. Kayisli, G. Luleci, and A. Arici In Vivo and In Vitro Regulation of Akt Activation in Human Endometrial Cells Is Estrogen Dependent Biol Reprod, September 1, 2004; 71(3): 714 - 721. [Abstract] [Full Text] [PDF] |
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Y. Wang, N. Ahmad, M. Kudo, and M. Ashraf Contribution of Akt and endothelial nitric oxide synthase to diazoxide-induced late preconditioning Am J Physiol Heart Circ Physiol, September 1, 2004; 287(3): H1125 - H1131. [Abstract] [Full Text] [PDF] |
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P. A. Ortiz, N. J. Hong, and J. L. Garvin Luminal flow induces eNOS activation and translocation in the rat thick ascending limb. II. Role of PI3-kinase and Hsp90 Am J Physiol Renal Physiol, August 1, 2004; 287(2): F281 - F288. [Abstract] [Full Text] [PDF] |
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D. Fulton, R. Babbitt, S. Zoellner, J. Fontana, L. Acevedo, T. J. McCabe, Y. Iwakiri, and W. C. Sessa Targeting of Endothelial Nitric-oxide Synthase to the Cytoplasmic Face of the Golgi Complex or Plasma Membrane Regulates Akt- Versus Calcium-dependent Mechanisms for Nitric Oxide Release J. Biol. Chem., July 16, 2004; 279(29): 30349 - 30357. [Abstract] [Full Text] [PDF] |
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R. I. Fernando and J. Wimalasena Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt Mol. Biol. Cell, July 1, 2004; 15(7): 3266 - 3284. [Abstract] [Full Text] [PDF] |
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W. C. Sessa eNOS at a glance J. Cell Sci., May 15, 2004; 117(12): 2427 - 2429. [Full Text] [PDF] |
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F. Barletta, C.-W. Wong, C. McNally, B. S. Komm, B. Katzenellenbogen, and B. J. Cheskis Characterization of the Interactions of Estrogen Receptor and MNAR in the Activation of cSrc Mol. Endocrinol., May 1, 2004; 18(5): 1096 - 1108. [Abstract] [Full Text] [PDF] |
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M. Esfandiarei, H. Luo, B. Yanagawa, A. Suarez, D. Dabiri, J. Zhang, and B. M. McManus Protein Kinase B/Akt Regulates Coxsackievirus B3 Replication through a Mechanism Which Is Not Caspase Dependent J. Virol., April 15, 2004; 78(8): 4289 - 4298. [Abstract] [Full Text] [PDF] |
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J. M. Orshal and R. A. Khalil Gender, sex hormones, and vascular tone Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R233 - R249. [Abstract] [Full Text] [PDF] |
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F. L. Wynne, J. A. Payne, A. E. Cain, J. F. Reckelhoff, and R. A. Khalil Age-Related Reduction in Estrogen Receptor-Mediated Mechanisms of Vascular Relaxation in Female Spontaneously Hypertensive Rats Hypertension, February 1, 2004; 43(2): 405 - 412. [Abstract] [Full Text] [PDF] |
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Y. Xu, R. J. Traystman, P. D. Hurn, and M. M. Wang Membrane Restraint of Estrogen Receptor {alpha} Enhances Estrogen-Dependent Nuclear Localization and Genomic Function Mol. Endocrinol., January 1, 2004; 18(1): 86 - 96. [Abstract] [Full Text] [PDF] |
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D.-b. Chen, I. M. Bird, J. Zheng, and R. R. Magness Membrane Estrogen Receptor-Dependent Extracellular Signal-Regulated Kinase Pathway Mediates Acute Activation of Endothelial Nitric Oxide Synthase by Estrogen in Uterine Artery Endothelial Cells Endocrinology, January 1, 2004; 145(1): 113 - 125. [Abstract] [Full Text] [PDF] |
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P.-F. Chen and K. K. Wu Structural Elements Contribute to the Calcium/Calmodulin Dependence on Enzyme Activation in Human Endothelial Nitric-oxide Synthase J. Biol. Chem., December 26, 2003; 278(52): 52392 - 52400. [Abstract] [Full Text] [PDF] |
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C. S. Watson and B. Gametchu Proteins of Multiple Classes May Participate in Nongenomic Steroid Actions Experimental Biology and Medicine, December 1, 2003; 228(11): 1272 - 1281. [Abstract] [Full Text] [PDF] |
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S. L. Liu, S. Schmuck, J. Z. Chorazcyzewski, R. Gros, and R. D. Feldman Aldosterone Regulates Vascular Reactivity: Short-Term Effects Mediated by Phosphatidylinositol 3-Kinase-Dependent Nitric Oxide Synthase Activation Circulation, November 11, 2003; 108(19): 2400 - 2406. [Abstract] [Full Text] [PDF] |
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D. P. Holden, J. E. Cartwright, S. S. Nussey, and G. S. J. Whitley Estrogen Stimulates Dimethylarginine Dimethylaminohydrolase Activity and the Metabolism of Asymmetric Dimethylarginine Circulation, September 30, 2003; 108(13): 1575 - 1580. [Abstract] [Full Text] [PDF] |
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S. Takahashi and M. E. Mendelsohn Synergistic Activation of Endothelial Nitric-oxide Synthase (eNOS) by HSP90 and Akt: CALCIUM-INDEPENDENT eNOS ACTIVATION INVOLVES FORMATION OF AN HSP90-Akt-CaM-BOUND eNOS COMPLEX J. Biol. Chem., August 15, 2003; 278(33): 30821 - 30827. [Abstract] [Full Text] [PDF] |
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K. Sasaki, M. Sato, and Y. Umezawa Fluorescent Indicators for Akt/Protein Kinase B and Dynamics of Akt Activity Visualized in Living Cells J. Biol. Chem., August 15, 2003; 278(33): 30945 - 30951. [Abstract] [Full Text] [PDF] |
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R. Chatrath, K. L. Ronningen, S. R. Severson, P. LaBreche, M. Jayachandran, M. P. Bracamonte, and V. M. Miller Endothelium-dependent responses in coronary arteries are changed with puberty in male pigs Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1168 - H1176. [Abstract] [Full Text] [PDF] |
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R. M. LOSEL, E. FALKENSTEIN, M. FEURING, A. SCHULTZ, H.-C. TILLMANN, K. ROSSOL-HASEROTH, and M. WEHLING Nongenomic Steroid Action: Controversies, Questions, and Answers Physiol Rev, July 1, 2003; 83(3): 965 - 1016. [Abstract] [Full Text] [PDF] |
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G. E. Stoica, T. F. Franke, A. Wellstein, F. Czubayko, H.-J. List, R. Reiter, E. Morgan, M. B. Martin, and A. Stoica Estradiol Rapidly Activates Akt via the ErbB2 Signaling Pathway Mol. Endocrinol., May 1, 2003; 17(5): 818 - 830. [Abstract] [Full Text] [PDF] |
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L. Li, M. P. Haynes, and J. R. Bender Plasma membrane localization and function of the estrogen receptor alpha variant (ER46) in human endothelial cells PNAS, April 15, 2003; 100(8): 4807 - 4812. [Abstract] [Full Text] [PDF] |
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R. Barsacchi, C. Perrotta, S. Bulotta, S. Moncada, N. Borgese, and E. Clementi Activation of Endothelial Nitric-Oxide Synthase by Tumor Necrosis Factor-alpha : A Novel Pathway Involving Sequential Activation of Neutral Sphingomyelinase, Phosphatidylinositol-3' kinase, and Akt Mol. Pharmacol., April 1, 2003; 63(4): 886 - 895. [Abstract] [Full Text] [PDF] |
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P. Dan, J. C. Y. Cheung, D. R. L. Scriven, and E. D. W. Moore Epitope-dependent localization of estrogen receptoralpha , but not -beta , in en face arterial endothelium Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1295 - H1306. [Abstract] [Full Text] [PDF] |
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S. Takahashi and M. E. Mendelsohn Calmodulin-dependent and -independent Activation of Endothelial Nitric-oxide Synthase by Heat Shock Protein 90 J. Biol. Chem., March 7, 2003; 278(11): 9339 - 9344. [Abstract] [Full Text] [PDF] |
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R. Thuillier, Y. Wang, and M. Culty Prenatal Exposure to Estrogenic Compounds Alters the Expression Pattern of Platelet-Derived Growth Factor Receptors {alpha} and {beta} in Neonatal Rat Testis: Identification of Gonocytes as Targets of Estrogen Exposure Biol Reprod, March 1, 2003; 68(3): 867 - 880. [Abstract] [Full Text] [PDF] |
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H. Harada, K. P. Pavlick, I. N. Hines, D. J. Lefer, J. M. Hoffman, S. Bharwani, R. E. Wolf, and M. B. Grisham Sexual dimorphism in reduced-size liver ischemia and reperfusion injury in mice: Role of endothelial cell nitric oxide synthase PNAS, January 21, 2003; 100(2): 739 - 744. [Abstract] [Full Text] [PDF] |
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M. P. Haynes, L. Li, D. Sinha, K. S. Russell, K. Hisamoto, R. Baron, M. Collinge, W. C. Sessa, and J. R. Bender Src Kinase Mediates Phosphatidylinositol 3-Kinase/Akt-dependent Rapid Endothelial Nitric-oxide Synthase Activation by Estrogen J. Biol. Chem., January 17, 2003; 278(4): 2118 - 2123. [Abstract] [Full Text] [PDF] |
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G. A. Figtree, D. McDonald, H. Watkins, and K. M. Channon Truncated Estrogen Receptor {alpha} 46-kDa Isoform in Human Endothelial Cells: Relationship to Acute Activation of Nitric Oxide Synthase Circulation, January 7, 2003; 107(1): 120 - 126. [Abstract] [Full Text] [PDF] |
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I. Fleming and R. Busse Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R1 - R12. [Abstract] [Full Text] [PDF] |
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C. Stirone, S. P. Duckles, and D. N. Krause Multiple forms of estrogen receptor-alpha in cerebral blood vessels: regulation by estrogen Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E184 - E192. [Abstract] [Full Text] [PDF] |
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C. E. Ihionkhan, K. L. Chambliss, L. L. Gibson, L. D. Hahner, M. E. Mendelsohn, and P. W. Shaul Estrogen Causes Dynamic Alterations in Endothelial Estrogen Receptor Expression Circ. Res., November 1, 2002; 91(9): 814 - 820. [Abstract] [Full Text] [PDF] |
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K. L. Chambliss and P. W. Shaul Estrogen Modulation of Endothelial Nitric Oxide Synthase Endocr. Rev., October 1, 2002; 23(5): 665 - 686. [Abstract] [Full Text] [PDF] |
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A. W. WYATT, J. R. STEINERT, C. P. D. WHEELER-JONES, A. J. MORGAN, D. SUGDEN, J. D. PEARSON, L. SOBREVIA, and G. E. MANN Early activation of the p42/p44MAPK pathway mediates adenosine-induced nitric oxide production in human endothelial cells: a novel calcium-insensitive mechanism FASEB J, October 1, 2002; 16(12): 1584 - 1594. [Abstract] [Full Text] [PDF] |
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L. Bjornstrom and M. Sjoberg Signal Transducers and Activators of Transcription as Downstream Targets of Nongenomic Estrogen Receptor Actions Mol. Endocrinol., October 1, 2002; 16(10): 2202 - 2214. [Abstract] [Full Text] [PDF] |
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K. K. Koh Effects of estrogen on the vascular wall: vasomotor function and inflammation Cardiovasc Res, September 1, 2002; 55(4): 714 - 726. [Full Text] [PDF] |
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M.-H. Zou, X.-Y. Hou, C.-M. Shi, D. Nagata, K. Walsh, and R. A. Cohen Modulation by Peroxynitrite of Akt- and AMP-activated Kinase-dependent Ser1179 Phosphorylation of Endothelial Nitric Oxide Synthase J. Biol. Chem., August 30, 2002; 277(36): 32552 - 32557. [Abstract] [Full Text] [PDF] |
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