Responses of vascular smooth muscle cells to estrogen are dependent on balance between ERK and p38 MAPK pathway activities

Cheng, Bei; Jiang, Song; Zou, Yun; Wang, Qiao; Lei, Yueshan; Zhu, Caihong; Hu, Chengjun

doi:10.1016/j.ijcard.2008.02.017

Cited by 27 publications

(19 citation statements)

References 42 publications

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“…In contrast to our observations, Galluzzo et al provided evidence that 17␤-estradiol regulates the first steps of L6 myoblast differentiation through modulation of Akt and p38 MAPK via ER␣ [5]. Moreover, Cheng et al showed that the hormone induces in rat vascular smooth muscle cells ERK and p38 MAPK activation via ER␣ and ␤, respectively, which leads in turn to cell proliferation or apoptosis [35]. Clearly, further studies are required to understand the role of ERs in E2-dependent MAPK signaling in myoblasts.…”

Section: Discussioncontrasting

confidence: 99%

“…In this work, using the selective antagonist for classical ERs, ICI182780 (1 M), we demonstrated that such estrogen receptors are involved in ERK2 but not in p38 MAPK activation induced by E2. These observations were further confirmed when ER␣ was silenced and this abrogated ERK2 stimulation without affecting p38 MAPK activation by the estrogen, in agreement with various reports which demonstrated that ERK1/2 modulation by E2 is mediated by ER␣ in different cellular types [34][35][36]. When ER␤ expression was blocked, ERK2 and p38 MAPK activation by E2 was observed, showing that the ␤ isoform of ER is not involved in MAPKs signaling induced by the hormone in this cell line.…”

Section: Discussionsupporting

confidence: 91%

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Role of estrogen receptors, PKC and Src in ERK2 and p38 MAPK signaling triggered by 17β-estradiol in skeletal muscle cells

Ronda

Buitrago

Boland

2010

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 91%

Role of estrogen receptors, PKC and Src in ERK2 and p38 MAPK signaling triggered by 17β-estradiol in skeletal muscle cells

Ronda

Buitrago

Boland

2010

The Journal of Steroid Biochemistry and Molecular Biology

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“…17 The mechanisms underlying these effects are poorly described, implicating ERK/MAPKs and p38/SAPKs2 balance or PI3K-Akt and Src signaling, and cannot explain all the E2 effects. 47,49,50 Recently, although the mechanism involved has not been identified, it has been suggested that inhibition of Rho-Rock pathway in the central nervous system or in the vasculature might participate to the limitation of arterial contraction induced by E2. 51 The observation that E2-induced AMPK-mediated RhoA phosphorylation on Ser188 provides the molecular mechanism of these observed effects.…”

Section: Discussionmentioning

confidence: 99%

AMPK Alpha 1-Induced RhoA Phosphorylation Mediates Vasoprotective Effect of Estradiol

Gayard

Guilluy

Rousselle

et al. 2011

ATVB

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Objective-Estradiol (E2) mediates numerous beneficial effects assigned to estrogens, but whereas mechanisms have been described at the endothelial level, direct effects on vascular smooth muscle cells (VSMC) are poorly documented. As evidence accumulates regarding the role of RhoA in vascular pathophysiology and the benefit of RhoA-Rho associated protein kinase (Rock) pathway inhibition, we analyzed if E2 could inhibit it in VSMC. Methods and Results-We show that in VSMC, E2 inhibits the RhoA-Rock pathway in a time-and concentrationdependent manner. The inhibition of RhoA-Rock pathway results from E2-induced phosphorylation of the Ser188 of RhoA. Using pharmacological, transfection, and in vitro phosphorylation experiments, we demonstrate that AMP-activated protein kinase subunit alpha 1 (AMPK␣1) is activated by estrogen receptor stimulation and catalyzes RhoA phosphorylation induced by E2. Ex vivo, ovariectomy leads to an increase in the amplitude of phenylephrine-or serotonine-induced contractions of aortic rings in wild-type mice but not in AMPK␣1-knock-out mice or E2-supplemented animals. These functional effects were correlated with a reduced level of RhoA phosphorylation in the aorta of ovariectomized female, male, and AMPK␣1 knock-out mice. Conclusion-Our work thus defines AMPK␣1 as (1) a new kinase for RhoA and (2) Key Words: cell physiology Ⅲ g proteins Ⅲ signal transduction Ⅲ vasoconstriction Ⅲ estrogen I n the vasculature, RhoA and its downstream effector Rho associated protein kinase (Rock) have been shown to regulate processes such as vascular smooth muscle cell (VSMC) contraction, proliferation and differentiations, endothelial permeability, platelet activation, and leukocyte migration. 1 Accordingly, basal RhoA activity is required for homeostatic functions in physiological conditions, but its sustained overactivation has pathological consequences in the vascular system, particularly in VSMC. Activation of RhoAdependent pathways is involved in excessive contraction, and thereby increases blood pressure, but also in excessive cell growth and migration that participate in pathological cardiovascular remodeling. 2 Several regulatory proteins thus cooperate to provide a tight control of RhoA activity including RhoA exchange factors and RhoA GTPase activating proteins that control the GDP/GTP cycle, and Rho guanine dissociation inhibitor (RhoGDI) that sequesters RhoA in the cytosol. 3 In addition to this regulation and independently of GDP-GTP cycling, recent reports have proposed that phosphorylation/ dephosphorylation cycle also controls Rho protein activity. cAMP-and cyclic GMP-dependent protein kinases (PKA and PKG) phosphorylate RhoA on Ser188. 4,5 Both in vitro and in vivo experiments indicated that Ser188 phosphorylation of RhoA induces increased association to GDI leading to cytosolic accumulation of RhoA, 6 inhibition of RhoA-mediated target activation and functions 7 and vasodilation. 5 Recently, we showed that stimulation of angiotensin II type 2 receptor (AT 2 R) in VSMC induces RhoA ph...

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“…The interference among different MAPK family members has been demonstrated in several previous reports. 46,47 Overall, the dynamic balance between Erk1/2 and p38 may be crucial in determining cell fate. 48 To further ascertain the involvement of Erk1/2 pathways in the mechanical-biochemical sensing, parallel experiments were carried in the presence of U0126, a chemical inhibitor of Erk1/2.…”

Section: Vibration and Growth Factor Modulate Stem Cell Behaviorsmentioning

confidence: 99%

Dynamic Vibration Cooperates with Connective Tissue Growth Factor to Modulate Stem Cell Behaviors

Tong

Zerdoum

Duncan

et al. 2014

Tissue Engineering Part A

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Responses of vascular smooth muscle cells to estrogen are dependent on balance between ERK and p38 MAPK pathway activities

Cited by 27 publications

References 42 publications

Role of estrogen receptors, PKC and Src in ERK2 and p38 MAPK signaling triggered by 17β-estradiol in skeletal muscle cells

Role of estrogen receptors, PKC and Src in ERK2 and p38 MAPK signaling triggered by 17β-estradiol in skeletal muscle cells

AMPK Alpha 1-Induced RhoA Phosphorylation Mediates Vasoprotective Effect of Estradiol

Dynamic Vibration Cooperates with Connective Tissue Growth Factor to Modulate Stem Cell Behaviors

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