17β-Estradiol Prevents Programmed Cell Death in Cardiac Myocytes

Pelzer, Theo; Schümann, Michael; Neumann, Manfred; deJager, Tertia; Stimpel, Michael; Serfling, Edgar; Neyses, Ludwig

doi:10.1006/bbrc.2000.2073

Cited by 104 publications

(55 citation statements)

References 30 publications

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“…It reduces caspase-3 activation and decreases DNA strand breaks (35,36). Estrogen also reduces cardiac apoptosis through a reduction in pro-apoptotic nuclear factor-κB (NF-κB), and also through increased PI3K/Akt signaling (37,38). Interestingly, post ischemic estrogen compared to vehicle in this study also reduced myocardial necrosis as measured by coronary effluent LDH.…”

Section: Discussionmentioning

confidence: 60%

Postischemic Infusion of 17-β-Estradiol Protects Myocardial Function and Viability

Terrell

Crisostomo

Markel

et al. 2008

Journal of Surgical Research

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Background-Females demonstrate improved cardiac recovery after ischemia-reperfusion (I/R) injury compared to males. Attenuation of myocardial dysfunction with pre-ischemic estradiol suggests that estrogen may be an important mediator of this cardioprotection. However, it remains unclear whether post injury estradiol may have clinical potential in the treatment of acute myocardial infarction. We hypothesize that post-ischemic administration of 17β-estradiol will decrease myocardial I/R injury, and improve left ventricular cardiac function.

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Section: Discussionmentioning

confidence: 60%

Postischemic Infusion of 17-β-Estradiol Protects Myocardial Function and Viability

Terrell

Crisostomo

Markel

et al. 2008

Journal of Surgical Research

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“…The fodrin ␣-subunit of various cells has been shown to be cleaved in association with apoptosis, in particular, due to upregulation of caspase 3 (4,15,48). Several reports have demonstrated that estrogen may play an inhibitory role in apoptosis in endothelial cells, breast cancer cells, cardiac myocytes, prostate cells, and neuronal cells (30,32,41,43). Moreover, it has been noted that some enzymatic activities are elevated in postmenopausal women compared with normal healthy women (1,27).…”

Section: Discussionmentioning

confidence: 99%

Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands

Ishimaru

Arakaki

Omotehara

et al. 2006

Molecular and Cellular Biology

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Although tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy, the molecular mechanism responsible for tissue-specific apoptosis remains obscure. Here we show that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands caused by estrogen deficiency. RbAp48-inducible transfectant results in rapid apoptosis with p53 phosphorylation (Ser9) and ␣-fodrin cleavage. Reducing the expression of RbAp48 through small interfering RNA inhibits the apoptosis. Prominent RbAp48 expression with apoptosis was observed in the exocrine glands of C57BL/6 ovariectomized (OVX) mice but not in OVX estrogen receptor ␣ ؊/؊ , p53 ؊/؊ , and E2F-1 ؊/؊ mice. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands but not in other organs. These findings indicate that estrogen deficiency initiates p53-mediated apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women.

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“…Convergent signaling of these diverse pathways on Akt presumably reflects important cross talk between signal transduction mechanisms, as has been reported for estrogen-mediated stimulation of the IGF-I receptor pathway, 32 activation of the IGF-I receptor by estrogen-mediated stimulation of PI3-K, 33 and increased Akt activity in vitro after estradiol or IGF-I treatment of carcinoma cells. 34 Akt activation by estrogen could also be the basis for inhibition of apoptosis induced by staurosporine treatment of cultured cardiomyocytes 35 (J. Molkentin, personal communication, January 2001), especially given that cardiomyocytes possess functional estrogen receptors. 36,37 Functional benefits for the heart provided by estrogenic stimulation include cardioprotection from ischemia-reperfusion injury in ovariectomized rats, 38 inhibition of pressure overload-induced hypertrophy (L. DeWindt, personal communication, January 2001), and phenotypic rescue of transgenic mouse models of dilated cardiomyopathy (M. Sussman, unpublished results, 2000).…”

Section: Discussionmentioning

confidence: 99%

Myocardial Akt Activation and Gender

Camper-Kirby

Welch²,

Walker³

et al. 2001

Circulation Research

235

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Abstract-Cardiovascular disease risk is higher in men than women, but the basis for this discrepancy remains controversial. Estrogenic stimulation of the myocardium or isolated cardiomyocytes has been purported to exert multiple beneficial effects associated with inhibition of maladaptive responses to pathogenic insults. This report describes a significant difference between the sexes in myocardial activation of Akt, a protein kinase that regulates a broad range of physiological responses including metabolism, gene transcription, and cell survival. We find that young women possess higher levels of nuclear-localized phospho-Akt 473 relative to comparably aged men or postmenopausal women. Both localization of phospho-Akt 473 in myocardial nuclei of sexually mature female mice versus males and Akt kinase activity in nuclear extracts of hearts from female mice versus males are elevated. Cytosolic localization of phospho-forkhead, a downstream nuclear target of Akt, is also increased in female relative to male mice, suggesting a potential mechanism for cardioprotective nuclear signaling resulting from Akt activation. Phospho-Akt 473 levels and localization at cardiac nuclei are similarly increased in transgenic mice with myocardium-specific expression of insulin-like growth factor I, a proven stimulus for Akt activation. Phospho-Akt 473 is also localized to the nucleus of cultured cardiomyocytes after exposure to 17␤-estradiol or genistein (a phytoestrogen in soy protein-based diets), and neonatal exposure of litters to genistein elevated nuclear phospho-Akt 473 localization. The activation of Akt in a gender-dependent manner may help explain differences observed in cardiovascular disease risk between the sexes and supports the potential beneficial effects of estrogenic stimulation.

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17β-Estradiol Prevents Programmed Cell Death in Cardiac Myocytes

Cited by 104 publications

References 30 publications

Postischemic Infusion of 17-β-Estradiol Protects Myocardial Function and Viability

Postischemic Infusion of 17-β-Estradiol Protects Myocardial Function and Viability

Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands

Myocardial Akt Activation and Gender

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