Estrogen protects primary cortical neurons from glutamate toxicity

Singer, Cherie A.; Rogers, Keith L.; Strickland, Tamara M.; Dorsa, Daniel M.

doi:10.1016/0304-3940(96)12760-9

Cited by 300 publications

(182 citation statements)

References 17 publications

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“…However, exogenous estradiol protected both male and female cells. This finding is in agreement with previous reports that estradiol protects neurons in vitro from excitotoxins (Singer et al, 1996;.…”

Section: Discussionsupporting

confidence: 94%

Role of P450 Aromatase in Sex-Specific Astrocytic Cell Death

Liu

Hurn

Roselli

et al. 2006

J Cereb Blood Flow Metab

134

116

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Female animals are protected from ischemic brain damage relative to age-matched males, in part through protection provided by endogenous estradiol. In brain, estradiol is produced from testosterone by cytochrome P450 aromatase (cyp 19), a steroid synthetic enzyme present in astrocytes. We tested the hypothesis that astrocytes derived from neonatal female rat brain are less susceptible than male cells to oxygen-glucose deprivation (OGD), and that this endogenous protection is associated with enhanced aromatase activity. Primary cultured cortical astrocytes were prepared from male and female rat pups separately and grown to confluence in estrogen-free media. Cell death in response to OGD, alone or in combination with hydrogen peroxide, lipopolysaccharides, interleukin-1b, tissue necrosis factor-a, or nitric oxide (NO) donor diethylenetriamine/nitric oxide adduct (DETA/NO) was quantified as the ratio of propidium iodide to calcein AM-positive cells. Aromatase activity and cyp19 mRNA and protein levels were measured in cultures from each sex. Female astrocytes are more resistant to OGD and oxidant cell death induced by H 2 O 2 , but sustain greater cell death when inflammatory mediators are combined with OGD compared with OGD alone. Media transfer from female to male cells conferred protection against OGD-induced cell death. Aromatase activity and expression is greater in female than in male astrocytes. The aromatase inhibitor, Arimidex (100 nmol/L), abolishes sex differences in OGD-induced cell death, whereas treatment with 17b-estradiol (10 nmol/L) protects cells of either sex. We conclude that astrocytes isolated from neonatal cortex exhibit marked sex differences in sensitivity to OGD, in part because of enhanced aromatization and estradiol formation in female cells.

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Section: Discussionsupporting

confidence: 94%

Role of P450 Aromatase in Sex-Specific Astrocytic Cell Death

Liu

Hurn

Roselli

et al. 2006

J Cereb Blood Flow Metab

134

116

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“…These studies argue for a receptor involvement in mediating the neuroprotection by estrogens. The neuroprotective effect of E2 in in vitro models is attenuated by the ER antagonists tamoxifen or ICI 182,780 in some studies (Singer et al, 1996(Singer et al, , 1999Pike, 1999 but not in others (Green et al, 1997;Sawada et al, 1998;Weaver et al, 1997;Moosmann and Behl, 1999;. Regan and Guo, 1997).…”

Section: Estrogens and Neuroprotectionmentioning

confidence: 99%

Estrogen actions on mitochondria—Physiological and pathological implications

Simpkins

Yang

Sarkar

et al. 2008

Molecular and Cellular Endocrinology

135

105

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Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and other have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor β (ERβ) into the mitochondria where it mediates a number of estrogen actions on this vital organelle. ERβ is imported into the mitochondria, through tethering to cytosolic chaperone protein and/or through direct interaction with mitochondrial import proteins. In the mitochondria, ERβ can affect transcription of critical mitochondrial genes through the interaction with estrogen response elements (ERE) or through protein-protein interactions with mitochondrially imported transcription factors. The potent effects of estrogens on mitochondrial function, particularly during mitochondrial stress, argues for a role of estrogens in the treatment of mitochondrial defects in chronic neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) and more acute conditions of mitochondrial compromise, like cerebral ischemia and traumatic brain injury.

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“…Estrogens, in fact, control the function of several genes and proteins directly involved in cell cycle regulation, including cyclins, proto-oncogenes, and negative cell cycle regulators (Altucci et al, 1996;Dinda et al, 1997), although they are well known modulators of cell life and death in different cell types, including uterine epithelia (Pollard et al, 1987), breast cancer cells (Kyprianou et al, 1991), and neurons (Singer et al, 1996;Sawada et al, 2000). The cellular mechanism(s) mediating estrogen prevention of programmed cell death has not been clarified yet.…”

Section: Introductionmentioning

confidence: 99%

Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

Caporali

Imai

Altucci

et al. 2003

MBoC

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Estrogens control cell growth and viability in target cells via an interplay of genomic and extragenomicpathways not yet elucidated. Here, we show evidence that cell proliferation and survival are differentially regulated by estrogen in rat pituitary tumor PR1 cells. Pico-to femtomolar concentrations of 17␤-estradiol (E2) are sufficient to foster PR1 cell proliferation, whereas nanomolar concentrations of the same are needed to prevent cell death that occurs at a high rate in these cells in the absence of hormone. Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations. Similarly, the pure antiestrogen ICI 182,780 inhibits estrogen response element-dependent trans-activation and cell death more effectively than cyclin-cdk activity, G 1 -S transition, or DNA synthesis rate. In antiestrogen-treated and/or estrogen-deprived cells, death is due predominantly to apoptosis. Estrogeninduced cell survival, but not E2-dependent cell cycle progression, can be prevented by an inhibitor of c-Src kinase or by blockade of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway. These data indicate the coexistence of two distinguishable estrogen signaling pathways in PR1 cells, characterized by different functions and sensitivity to hormones and antihormones.

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Estrogen protects primary cortical neurons from glutamate toxicity

Cited by 300 publications

References 17 publications

Role of P450 Aromatase in Sex-Specific Astrocytic Cell Death

Role of P450 Aromatase in Sex-Specific Astrocytic Cell Death

Estrogen actions on mitochondria—Physiological and pathological implications

Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

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