Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

Tran, Quang‐Kim; Firkins, Rachel; Giles, Jennifer; Francis, Sarah; Matnishian, Vahe; Tran, Phuong; VerMeer, Mark; Jasurda, Jake; Burgard, Michelle; Gebert‐Oberle, Briana

doi:10.1074/jbc.m115.697334

Cited by 33 publications

(50 citation statements)

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“…Recurrent inflammatory factors are known to play a role in breast cancer promotion and angiogenesis . The observation of upregulation of pro‐inflammatory cytokines IL‐6, IL‐1 and TNF in ER‐positive tumors demonstrated that these cytokines play an important role in the activation of ER . Activated ER promotes the release of vasodilators, leading to vasomotor disorders and neovascularization .…”

Section: Discussionmentioning

confidence: 99%

“…35,36 The observation of upregulation of pro-inflammatory cytokines IL-6, IL-1 and TNF in ER-positive tumors demonstrated that these cytokines play an important role in the activation of ER. 50,51 Activated ER promotes the release of vasodilators, leading to vasomotor disorders and neovascularization. 52 Moreover, studies have shown that several autoimmune disorders are associated with ER-positive breast cancer, 52 suggesting a potential relationship between immune abnormalities and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

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Potential association between rosacea and cancer: A study in a medical center in southern China

Long

Yuan

et al. 2019

The Journal of Dermatology

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Growing evidence suggests that rosacea increases the risk of systemic diseases, but studies of the relationships between rosacea and cancer are rare. Aimed to assess the relationship between rosacea and cancer, a total of 7548 patients with confirmed internal malignancies and 8340 cancer‐free individuals aged 18 years or more were included in this study from November 2015 to October 2017. Clinical characteristics, personal history and laboratory data were recorded when patients were diagnosed with rosacea. Logistic regression analyses were performed to analyze associations between cancer and rosacea. We found rosacea significantly affected more women than men in both cancer and cancer‐free group. The data showed there was no relationship between rosacea and lung, gastrointestinal, nasopharyngeal and gynecological cancer. However, rosacea was significantly associated with the increased risk of breast cancer and glioma, but negatively associated with the risk of hematological cancer. Of the 190 female breast cancer patients with rosacea, 98.95% had the erythematotelangiectatic subtype of rosacea, 48.42% had chloasma and 76.31% of them were Fitzpatrick skin type III and IV. In our binary regression model, breast cancer patients with rosacea had a higher prevalence of estrogen receptor‐positive status, lower high‐density lipoprotein levels and higher low‐density lipoprotein than patients with breast cancer but no rosacea. Our findings indicate that rosacea is significantly associated with higher incidence of breast cancer, glioma and lower prevalence of hematological cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Potential association between rosacea and cancer: A study in a medical center in southern China

Long

Yuan

et al. 2019

The Journal of Dermatology

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“…As to G βγ initiated ERK1/2 transactivation, this cascade includes Src ‐mediated activation of matrix metalloproteinases (MMPs) accompanied by the release of heparin‐bound epidermal growth factor (EGF) and the activation of the EGF receptor (EGFR), followed by the activation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and phosphoinositide 3‐kinase (PI3K) . G βγ transactivation of ERK1/2 and PI3K can activate endothelial nitric oxide synthase (eNOS) in a mitogen‐activated protein kinase (MAPK)‐dependent manner . eNOS activation is followed by increased NO production which can recruit pain sensitizing molecules .…”

Section: Features Of Gpermentioning

confidence: 99%

New roles for neuronal estrogen receptors

Herndon

2017

Neurogastroenterology Motil

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Estrogens encompass steroid hormones which display physiological roles not only in the female reproductive system but also in other organ systems of non-reproductive controls, including the peripheral and central nervous systems. Traditionally, estrogen signals in neurons through a "genomic pathway": binding to estrogen receptors (ERs) which then interact with nuclear estrogen response elements to initiate transcription. This effect is usually delayed at onset (within several hours to days) and prolonged in duration. In addition to these classical ERs, recent data suggest that other ERs function through pregenomic signaling pathways. Estrogen's pregenomic pathways cause intracellular changes within seconds to minutes and go through a novel, 7-transmembrane spanning G protein-coupled receptor (GPER, formerly known as GPR30). In this review, we will briefly cover the cellular and molecular mechanisms of GPER and then discuss newly discovered roles of GPER in cognition, depression, homeostasis, pain processing, and other associated neuronal functions.

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“…In addition to changes in SERCA and PLB expression/phosphorylation profiles, the improvement in cardiac function with G1 treatment in these models could also be due in part to improvements in endothelial nitric oxide synthase (eNOS) activity and vascular tone. The effects of G1 on the vascular endothelium likely involve stimulation of Ca 2+ /calmodulin signaling network activities (87), including GPER activation per se (87,88), upregulation of the Ca 2+ -dependent interaction between eNOS and calmodulin (87), improvement in the eNOS phosphorylation profile (87,89), and optimization of vascular Ca 2+ signaling via combined effects on influx (90) and efflux pathways (91).…”

Section: Estrogen Gper and Serca2a And Its Regulatory Proteinsmentioning

confidence: 99%

Female Heart Health: Is GPER the Missing Link?

et al. 2020

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The G Protein-Coupled Estrogen Receptor (GPER) is a novel membrane-bound receptor that mediates non-genomic actions of the primary female sex hormone 17β-estradiol. Studies over the past two decades have elucidated the beneficial actions of this receptor in a number of cardiometabolic diseases. This review will focus specifically on the cardiac actions of GPER, since this receptor is expressed in cardiomyocytes as well as other cells within the heart and most likely contributes to estrogen-induced cardioprotection. Studies outlining the impact of GPER on diastolic function, mitochondrial function, left ventricular stiffness, calcium dynamics, cardiac inflammation, and aortic distensibility are discussed. In addition, recent data using genetic mouse models with global or cardiomyocyte-specific GPER gene deletion are highlighted. Since estrogen loss due to menopause in combination with chronological aging contributes to unique aspects of cardiac dysfunction in women, this receptor may provide novel therapeutic effects. While clinical studies are still required to fully understand the potential for pharmacological targeting of this receptor in postmenopausal women, this review will summarize the evidence gathered thus far on its likely beneficial effects.

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Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

Abstract: Estrogen exerts many effects on the vascular endothelium. Calmodulin (CaM) is the transducer of Ca 2؉ signals and is a limiting factor in cardiovascular tissues. It is unknown whether and how estrogen modifies endothelial functions via the net-

Cited by 33 publications

References 65 publications

Potential association between rosacea and cancer: A study in a medical center in southern China

Potential association between rosacea and cancer: A study in a medical center in southern China

New roles for neuronal estrogen receptors

Female Heart Health: Is GPER the Missing Link?

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