Differential effects of 17[3‐estradiol on mitogen‐activated protein kinasepathways in rat cardiomyocytes

Nuedling, Simone; Kahlert, Stefan; Loebbert, Kerstin; Meyer, Rainer; Vetter, Hans; Grohé, Christian

doi:10.1016/s0014-5793(99)00816-9

Cited by 66 publications

(13 citation statements)

References 36 publications

(36 reference statements)

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“…Since estrogen has been shown to rapidly activate both the MAPK and PI3K signaling pathways in cardiac myocytes and other cell types [29, 41], we next asked whether any ERα-EGFP variant was capable of rapid activation of either of these pathways in isolated cardiac myocytes. To this end, neonatal-RVMs were infected with corresponding adenoviruses and treated briefly (5 minutes) with 100 pM estrogen or vehicle.…”

Section: Resultsmentioning

confidence: 99%

“…When overexpressed in HEK293 (Human Embryonic Kidney) cells or MCF7 breast cancer cells ERα36 has been shown to regulate rapid signaling pathways such as the pERK/MAPK pathway [28]. The demonstrated ability of cardiac myocytes to also respond rapidly to estrogen treatment through activation of analogous pERK/MAPK signaling [29] and the importance of the pERK/MAPK pathway in regulating cardiac myocyte biology [30, 31] call for a more thorough investigation of the ability of specific ERα isoforms to regulate these pathways in cardiac myocytes.…”

Section: Introductionmentioning

confidence: 99%

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Estrogen receptor profiling and activity in cardiac myocytes

Pugach

Blenck

Dragavon

et al. 2016

Molecular and Cellular Endocrinology

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Estrogen signaling appears critical in the heart. However a mechanistic understanding of the role of estrogen in the cardiac myocyte is lacking. Moreover, there are multiple cell types in the heart and multiple estrogen receptor (ER) isoforms. Therefore, we studied expression, localization, transcriptional and signaling activity of ERs in isolated cardiac myocytes. We found only ERα RNA (but no ERβ RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ERα protein (ERα66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ERα encoded by the same genomic locus (ERα46 and ERα36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ERα isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ERα at the level of transcription in cardiac myocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estrogen receptor profiling and activity in cardiac myocytes

Pugach

Blenck

Dragavon

et al. 2016

Molecular and Cellular Endocrinology

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“…In one study, 5 minute or longer treatment of adult cardiomyocytes with 1 nM E2 failed to show a significant increase in p38 MAPK phosphorylation either through Western blot analysis or phosphorylation assay, whereas activation of ERK1/2 and JNK was observed [17]. Furthermore, a comparison of female wild-type and ERα knockout mice showed no difference in p38 MAPK activation, but an increase in protective ERK1/2 and a decrease in JNK activation during ischemia [31].…”

Section: Discussionmentioning

confidence: 99%

“…Despite its known cardioprotective effects, the intracellular mechanisms by which ERα regulates myocardial function has not been fully elucidated. p38 MAPK has been implicated in E2-mediated signaling in the heart and the cardioprotective effects of ERα activation [16], [17], but no studies have examined the links between the ERα and p38 MAPK under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Rapid Changes in Cardiac Myofilament Function following the Acute Activation of Estrogen Receptor-Alpha

2012

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Estrogens have well-recognized and complex cardiovascular effects, including altering myocardial contractility through changes in myofilament function. The presence of multiple estrogen receptor (ER) isoforms in the heart may explain some discrepant findings about the cardiac effects of estrogens. Most studies examining the impact of estrogens on the heart have focused on chronic changes in estrogen levels, and have not investigated rapid, non-genomic pathways. The first objective of this study was to determine how acute activation of ERα impacts cardiac myofilaments. Nongenomic myocardial estrogen signaling is associated with the activation of a variety of signaling pathways. p38 MAPK has been implicated in acute ER signaling in the heart, and is known to affect myofilament function. Thus, the second objective of this study was to determine if acute ERα activation mediates its myofilament effects through p38 MAPK recruitment. Hearts from female C57Bl/6 mice were perfused with the ERα agonist PPT and myofilaments isolated. Activation of ERα depressed actomyosin MgATPase activity and decreased myofilament calcium sensitivity. Inhibition of p38 MAPK attenuated the myofilament effects of ERα activation. ERα stimulation did not affect global myofilament protein phosphorylation, but troponin I phosphorylation at the putative PKA phosphorylation sites was decreased. Changes in myofilament activation did not translate into alterations in whole heart function. The present study provides evidence supporting rapid, non-genomic changes in cardiac myofilament function following acute ERα stimulation mediated by the p38 MAPK pathway.

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“…There is evidence that atherosclerosis involves an ongoing inflammatory response, which is more profound during the early years of menopause [40,51,52]. Cytokine production has been shown to increase in the early years following menopause but thereafter declines to within the premenopausal range [52,53 • ].…”

Section: Hormonal Replacement Therapymentioning

confidence: 99%

Estrogen, hormonal replacement therapy and cardiovascular disease

Yang

Reckelhoff

2011

Current Opinion in Nephrology &Amp; Hypertension

229

150

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Purpose of review Premenopausal women have a lower risk and incidence of hypertension and cardiovascular disease (CVD) compared to age-matched men and this sex advantage for women gradually disappears after menopause, suggesting that sexual hormones play a cardioprotective role in women. However, randomized prospective primary or secondary prevention trials failed to confirm that hormone replacement therapy (HRT) affords cardioprotection. This review highlights the factors that may contribute to this divergent outcome and could reveal why young or premenopausal women are protected from CVD and yet postmenopausal women do not benefit from HRT. Recent findings In addition to the two classical estrogen receptors, ERα and ERβ, a third, G-protein-coupled estrogen receptor GPR30, has been identified. New intracellular signaling pathways and actions for the cardiovascular protective properties of estrogen have been proposed. In addition, recent Women’s Health Initiative (WHI) studies restricted to younger postmenopausal women showed that initiation of HRT closer to menopause reduced the risk of CVD. Moreover, dosage, duration, the type of estrogen and route of administration all merit consideration when determining the outcome of HRT. Summary HRT has become one of the most controversial topics related to women’s health. Future studies are necessary if we are to understand the divergent published findings regarding HRT and develop new therapeutic strategies to improve the quality of life for women.

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Differential effects of 17[3‐estradiol on mitogen‐activated protein kinasepathways in rat cardiomyocytes

Cited by 66 publications

References 36 publications

Estrogen receptor profiling and activity in cardiac myocytes

Estrogen receptor profiling and activity in cardiac myocytes

Rapid Changes in Cardiac Myofilament Function following the Acute Activation of Estrogen Receptor-Alpha

Estrogen, hormonal replacement therapy and cardiovascular disease

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