GPER mediates the effects of 17β-estradiol in cardiac mitochondrial biogenesis and function

Sbert-Roig, Miquel; Bauzá-Thorbrügge, Marco; Galmés-Pascual, Bel M.; Capllonch-Amer, Gabriela; García-Palmer, Francisco J.; Lladó, Isabel; Proenza, Ana M.; Gianotti, Magdalena

doi:10.1016/j.mce.2015.11.027

Cited by 51 publications

(37 citation statements)

References 51 publications

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“…The protective effects of estrogens might be mediated, at least partially, by GPER, since activation of GPER by G1 inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury [28]. More recently, studies in H9c2 cardiomyocytes have shown that G1 mimics the beneficial actions of estradiol on enhancing mitochondrial function and biogenesis, while the GPER antagonist G15 neutralizes the beneficial effects on bioenergetics [42]. Although confirmation of any alterations in mitochondrial structure and function between cardiomyocyte-specific GPER KO vs. WT mice will require further study, our microarray data and GSEA provided direct evidence that the cardioprotective effects of GPER in the female might be related to enhancements in mitochondrial function.…”

Section: 0 Discussionmentioning

confidence: 99%

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis

Wang

Sun

Chou

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Activation of G protein-coupled estrogen receptor (GPER) by its agonist, G1, protects the heart from stressors such as pressure-overload, ischemia, a high-salt diet, estrogen loss, and aging, in various male and female animal models. Due to nonspecific effects of G1, the exact functions of cardiac GPER cannot be concluded from studies using systemic G1 administration. Moreover, global knockdown of GPER affects glucose homeostasis, blood pressure, and many other cardiovascular-related systems, thereby confounding interpretation of its direct cardiac actions. We generated a cardiomyocyte-specific GPER knockout (KO) mouse model to specifically investigate the functions of GPER in cardiomyocytes. Compared to wild type mice, cardiomyocyte-specific GPER KO mice exhibited adverse alterations in cardiac structure and impaired systolic and diastolic function, as measured by echocardiography. Gene deletion effects on left ventricular dimensions were more profound in male KO mice compared to female KO mice. Analysis of DNA microarray data from isolated cardiomyocytes of wild type and KO mice revealed sex-based differences in gene expression profiles affecting multiple transcriptional networks. Gene Set Enrichment Analysis (GSEA) revealed that mitochondrial genes are enriched in GPER KO females, whereas inflammatory response genes are enriched in GPER KO males, compared to their wild type counterparts of the same sex. The cardiomyocyte-specific GPER KO mouse model provides us with a powerful tool to study the functions of GPER in cardiomyocytes. The gene expression profiles of the GPER KO mice provide foundational information for further study of the mechanisms underlying sex-specific cardioprotection by GPER.

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Section: 0 Discussionmentioning

confidence: 99%

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis

Wang

Sun

Chou

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Furthermore, reduced levels of estrogens, such as in ovariectomized mice, lead to increased ROS production. 154 Estrogens (Figure 5) can bind to the transcription factors estrogen receptor α (ERα) and estrogen receptor β (ERβ) to directly influence gene expression. 17β-Estradiol ( 14 ) 155 and progesterone ( 15 ) 156 are the principle biologically active estrogens.…”

Section: Transcription Factor Modulatorsmentioning

confidence: 99%

“…Additionally, at least a portion of the cardioprotective effects of estrogen are mediated through the GPER, as shown by stimulation with the GPER-selective agonist 18 . 154 Despite the clear protective potential of estrogens, their proliferative and endocrine effects limit their use as a long-term therapy for chronic degenerative diseases. However, the development of selective ER and GPER ligands that drive specific signaling and transcriptional programs may improve the utility of such therapeutics.…”

Section: Transcription Factor Modulatorsmentioning

confidence: 99%

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

2016

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Mitochondria have various roles in cellular metabolism and homeostasis. Because mitochondrial dysfunction is associated with many acute and chronic degenerative diseases, mitochondrial biogenesis (MB) is a therapeutic target for treating such diseases. Here, we review the role of mitochondrial dysfunction in acute and chronic degenerative diseases and the cellular signaling pathways by which MB is induced. We then review existing work describing the development and application of drugs that induce MB in vitro and in vivo. In particular, we discuss natural products and modulators of transcription factors, kinases, cyclic nucleotides, and G protein-coupled receptors.

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“…Taken together, these studies suggest that the relationship between prohibitins and estrogen is complex and both may regulate each other's function in the maintenance of adipose tissue homeostasis, and their dysregulation may lead to obesity development. Of note, estrogen is known to have a role in cardiac mitochondrial biogenesis and function [58]. However, it remains to be clarified whether the role of estrogen in mitochondrial biology underlies its role in adipose tissue and metabolic homeostasis.…”

Section: Interplay Between Estrogen and Phb In Adipose Tissue Homeostmentioning

confidence: 99%

Prohibitin in Adipose and Immune Functions

Ande

Nguyen

Nyomba

et al. 2016

Trends in Endocrinology & Metabolism

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GPER mediates the effects of 17β-estradiol in cardiac mitochondrial biogenesis and function

Cited by 51 publications

References 51 publications

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis

Cardiomyocyte-specific deletion of the G protein-coupled estrogen receptor (GPER) leads to left ventricular dysfunction and adverse remodeling: A sex-specific gene profiling analysis

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

Prohibitin in Adipose and Immune Functions

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