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Jeffrey R Bender - One of the best experts on this subject based on the ideXlab platform.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells effects on calcium sensitivity and no release
    Journal of Biological Chemistry, 2000
    Co-Authors: Kerry S Russell, Page M Haynes, William C Sessa, Teresa Caulinglaser, James Rosneck, Jeffrey R Bender
    Abstract:

    Estradiol (E(2)) causes endothelium-dependent vasodilation, mediated, in part, by enhanced nitric oxide (NO) release. We have previously shown that E(2)-induced activation of endothelial nitric oxide synthase (eNOS) reduces its calcium dependence. This pathway of eNOS activation is unique to a limited number of stimuli, including shear stress, the response to which is herbimycin-inhibitable. Consistent with this, herbimycin and geldanamycin pretreatment of human umbilical vein endothelial cells (HUVEC) abrogated E(2)-stimulated NO release and cGMP production, respectively. These benzoquinone ansamycins are potent inhibitors of Hsp90 function, which has recently been shown to play a role in stimulus-dependent eNOS activation. As in response to shear, E(2) induced an Hsp90-eNOS association, peaking at 30 min and completely inhibited by the conventional Estrogen Receptor Antagonist ICI 182,780. These findings suggest that Hsp90 plays an important role in the rapid, Estrogen Receptor-mediated modulation of eNOS activation by Estrogen.

Pieter A Doevendans - One of the best experts on this subject based on the ideXlab platform.

  • 17β estradiol antagonizes cardiomyocyte hypertrophy by autocrine paracrine stimulation of a guanylyl cyclase a Receptor cyclic guanosine monophosphate dependent protein kinase pathway
    Circulation, 2004
    Co-Authors: Fawzi A Babiker, Leon J De Windt, Martin Van Eickels, Victor L Thijssen, R Bronsaer, C Grohe, Marc Van Bilsen, Pieter A Doevendans
    Abstract:

    BACKGROUND: Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17beta-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an Antagonistic role for E2 in this process, although no molecular mechanism has been proposed for this phenomenon. METHODS AND RESULTS: E2 attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF) expression as assessed by Northern blot, immunocytochemical analyses, and transient transfection assays using ANF promoter deletion fragments. Both the antihypertrophic effects and ANF induction could be blocked by the Estrogen Receptor Antagonist ICI 182,780, which demonstrates a genomic, Estrogen Receptor-dependent pathway. To mimic E2-induced autocrine/paracrine effects through stimulation of the guanylyl cyclase A Receptor (ANF Receptor), cardiomyocytes were stimulated with phenylephrine or endothelin-1 in the presence of exogenous ANF or 8-bromo-cyclic guanosine monophosphate (cGMP), both of which attenuated agonist-induced hypertrophy. Both Estrogen and ANF increased cGMP activity. The antihypertrophic effect of ANF could be reduced with extracellular ANF antibodies in a dose-dependent manner. cGMP-dependent protein kinase mediates the antihypertrophic effects of E2, so cardiomyocytes were agonist stimulated in the presence of the cGMP-dependent protein kinase blocker KT-5823. KT-5823 not only reversed the antihypertrophic properties of E2, ANF, or 8-bromo-cGMP, but also evoked potentiation of hypertrophy. CONCLUSIONS: E2-mediated induction of ANF in cardiac hypertrophy contributes to its Antagonistic effects in LVH.

  • 17β estradiol antagonizes cardiomyocyte hypertrophy by autocrine paracrine stimulation of a guanylyl cyclase a Receptor cyclic guanosine monophosphate dependent protein kinase pathway
    Circulation, 2004
    Co-Authors: Fawzi A Babiker, Leon J De Windt, Victor L Thijssen, R Bronsaer, C Grohe, Martin Van Eickels, Marc Van Bilsen, Pieter A Doevendans
    Abstract:

    Background— Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17β-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an Antagonistic role for E2 in this process, although no molecular mechanism has been proposed for this phenomenon. Methods and Results— E2 attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF) expression as assessed by Northern blot, immunocytochemical analyses, and transient transfection assays using ANF promoter deletion fragments. Both the antihypertrophic effects and ANF induction could be blocked by the Estrogen Receptor Antagonist ICI 182,780, which demonstrates a genomic, Estrogen Receptor-dependent pathway. To mimic E2-induced autocrine/paracrine effects through stimulation of the guanylyl cyclase A Receptor (ANF Receptor), cardiomyocytes were stimulated with phenyle...

Page M Haynes - One of the best experts on this subject based on the ideXlab platform.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells effects on calcium sensitivity and no release
    Journal of Biological Chemistry, 2000
    Co-Authors: Kerry S Russell, Page M Haynes, William C Sessa, Teresa Caulinglaser, James Rosneck, Jeffrey R Bender
    Abstract:

    Estradiol (E(2)) causes endothelium-dependent vasodilation, mediated, in part, by enhanced nitric oxide (NO) release. We have previously shown that E(2)-induced activation of endothelial nitric oxide synthase (eNOS) reduces its calcium dependence. This pathway of eNOS activation is unique to a limited number of stimuli, including shear stress, the response to which is herbimycin-inhibitable. Consistent with this, herbimycin and geldanamycin pretreatment of human umbilical vein endothelial cells (HUVEC) abrogated E(2)-stimulated NO release and cGMP production, respectively. These benzoquinone ansamycins are potent inhibitors of Hsp90 function, which has recently been shown to play a role in stimulus-dependent eNOS activation. As in response to shear, E(2) induced an Hsp90-eNOS association, peaking at 30 min and completely inhibited by the conventional Estrogen Receptor Antagonist ICI 182,780. These findings suggest that Hsp90 plays an important role in the rapid, Estrogen Receptor-mediated modulation of eNOS activation by Estrogen.

Fawzi A Babiker - One of the best experts on this subject based on the ideXlab platform.

  • 17β estradiol antagonizes cardiomyocyte hypertrophy by autocrine paracrine stimulation of a guanylyl cyclase a Receptor cyclic guanosine monophosphate dependent protein kinase pathway
    Circulation, 2004
    Co-Authors: Fawzi A Babiker, Leon J De Windt, Martin Van Eickels, Victor L Thijssen, R Bronsaer, C Grohe, Marc Van Bilsen, Pieter A Doevendans
    Abstract:

    BACKGROUND: Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17beta-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an Antagonistic role for E2 in this process, although no molecular mechanism has been proposed for this phenomenon. METHODS AND RESULTS: E2 attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF) expression as assessed by Northern blot, immunocytochemical analyses, and transient transfection assays using ANF promoter deletion fragments. Both the antihypertrophic effects and ANF induction could be blocked by the Estrogen Receptor Antagonist ICI 182,780, which demonstrates a genomic, Estrogen Receptor-dependent pathway. To mimic E2-induced autocrine/paracrine effects through stimulation of the guanylyl cyclase A Receptor (ANF Receptor), cardiomyocytes were stimulated with phenylephrine or endothelin-1 in the presence of exogenous ANF or 8-bromo-cyclic guanosine monophosphate (cGMP), both of which attenuated agonist-induced hypertrophy. Both Estrogen and ANF increased cGMP activity. The antihypertrophic effect of ANF could be reduced with extracellular ANF antibodies in a dose-dependent manner. cGMP-dependent protein kinase mediates the antihypertrophic effects of E2, so cardiomyocytes were agonist stimulated in the presence of the cGMP-dependent protein kinase blocker KT-5823. KT-5823 not only reversed the antihypertrophic properties of E2, ANF, or 8-bromo-cGMP, but also evoked potentiation of hypertrophy. CONCLUSIONS: E2-mediated induction of ANF in cardiac hypertrophy contributes to its Antagonistic effects in LVH.

  • 17β estradiol antagonizes cardiomyocyte hypertrophy by autocrine paracrine stimulation of a guanylyl cyclase a Receptor cyclic guanosine monophosphate dependent protein kinase pathway
    Circulation, 2004
    Co-Authors: Fawzi A Babiker, Leon J De Windt, Victor L Thijssen, R Bronsaer, C Grohe, Martin Van Eickels, Marc Van Bilsen, Pieter A Doevendans
    Abstract:

    Background— Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17β-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an Antagonistic role for E2 in this process, although no molecular mechanism has been proposed for this phenomenon. Methods and Results— E2 attenuated phenylephrine and endothelin-1 induced hypertrophy in neonatal cardiomyocytes, and E2 directly induced atrial natriuretic factor (ANF) expression as assessed by Northern blot, immunocytochemical analyses, and transient transfection assays using ANF promoter deletion fragments. Both the antihypertrophic effects and ANF induction could be blocked by the Estrogen Receptor Antagonist ICI 182,780, which demonstrates a genomic, Estrogen Receptor-dependent pathway. To mimic E2-induced autocrine/paracrine effects through stimulation of the guanylyl cyclase A Receptor (ANF Receptor), cardiomyocytes were stimulated with phenyle...

Kerry S Russell - One of the best experts on this subject based on the ideXlab platform.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • membrane Estrogen Receptor engagement activates endothelial nitric oxide synthase via the pi3 kinase akt pathway in human endothelial cells
    Circulation Research, 2000
    Co-Authors: Page M Haynes, Diviya Sinha, Kerry S Russell, Mark Collinge, David J Fulton, Manuel Moralesruiz, William C Sessa, Jeffrey R Bender
    Abstract:

    Abstract —17β-Estradiol (E2) is a rapid activator of endothelial nitric oxide synthase (eNOS). The product of this activation event, NO, is a fundamental determinant of cardiovascular homeostasis. We previously demonstrated that E2-stimulated endothelial NO release can occur without an increase in cytosolic Ca2+. Here we demonstrate for the first time, to our knowledge, that E2 rapidly induces phosphorylation and activation of eNOS through the phosphatidylinositol 3 (PI3)-kinase–Akt pathway. E2 treatment (10 ng/mL) of the human endothelial cell line, EA.hy926, resulted in increased NO production, which was abrogated by the PI3-kinase inhibitor, LY294002, and the Estrogen Receptor Antagonist ICI 182,780. E2 stimulated rapid Akt phosphorylation on serine 473. As has been shown for vascular endothelial growth factor, eNOS is an E2-activated Akt substrate, demonstrated by rapid eNOS phosphorylation on serine 1177, a critical residue for eNOS activation and enhanced sensitivity to resting cellular Ca2+ levels. Adenoviral-mediated EA.hy926 transduction confirmed functional involvement of Akt, because a kinase-deficient, dominant-negative Akt abolished E2-stimulated NO release. The membrane-impermeant E2BSA conjugate, shown to bind endothelial cell membrane sites, also induced rapid Akt and consequent eNOS phosphorylation. Thus, engagement of membrane Estrogen Receptors results in rapid endothelial NO release through a PI3-kinase–Akt-dependent pathway. This explains, in part, the reduced requirement for cytosolic Ca2+ fluxes and describes an important pathway relevant to cardiovascular pathophysiology.

  • Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells effects on calcium sensitivity and no release
    Journal of Biological Chemistry, 2000
    Co-Authors: Kerry S Russell, Page M Haynes, William C Sessa, Teresa Caulinglaser, James Rosneck, Jeffrey R Bender
    Abstract:

    Estradiol (E(2)) causes endothelium-dependent vasodilation, mediated, in part, by enhanced nitric oxide (NO) release. We have previously shown that E(2)-induced activation of endothelial nitric oxide synthase (eNOS) reduces its calcium dependence. This pathway of eNOS activation is unique to a limited number of stimuli, including shear stress, the response to which is herbimycin-inhibitable. Consistent with this, herbimycin and geldanamycin pretreatment of human umbilical vein endothelial cells (HUVEC) abrogated E(2)-stimulated NO release and cGMP production, respectively. These benzoquinone ansamycins are potent inhibitors of Hsp90 function, which has recently been shown to play a role in stimulus-dependent eNOS activation. As in response to shear, E(2) induced an Hsp90-eNOS association, peaking at 30 min and completely inhibited by the conventional Estrogen Receptor Antagonist ICI 182,780. These findings suggest that Hsp90 plays an important role in the rapid, Estrogen Receptor-mediated modulation of eNOS activation by Estrogen.