Low concentrations of estradiol reduce β-amyloid (25–35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells

Gridley, Kelly E.; Green, Pattie S.; Simpkins, James W.

doi:10.1016/s0006-8993(97)01056-1

Cited by 122 publications

(57 citation statements)

References 42 publications

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“…The antioxidant actions of estrogen on cell membranes are ER-independent, and the phenolic A-ring structure may play an important role in this effect. Mounting evidence shows that estradiol inhibits lipid peroxidation (Behl et al, 1995;Goodman et al, 1996;Gridley et al, 1997). Sugioka et al (1987) first postulated that the phenolic A-ring is closely related with the effect of estrogen on inhibiting lipid peroxidation.…”

Section: Estrogens and Mitochondrial Functionmentioning

confidence: 99%

“…In addition, estrogen therapy is associated with decreased incidence and enhanced recovery from ischemic stroke. In in vitro studies, protective effects of estrogen have been widely reported in different types of neuronal cells against a variety of insults, including H 2 O 2 (Behl et al, 1995(Behl et al, , 1997Sawada et al, 1998;Singer et al, 1998;Moosmann and Behl, 1999;, serum deprivation (Bishop and Simpkins, 1994;Green et al, 1997a,b;Bae et al, 2000), oxygen-glucose deprivation (Regan and Guo, 1997;Wilson et al, 2000), iron (Goodman et al, 1996;Blum-Degen et al, 1998), amyloid ␤ peptide-induced toxicity (Behl et al, 1995(Behl et al, , 1997Green et al, 1996;Gridley et al, 1997;Mattson et al, 1997;Pike, 1999), excitotoxicity (Goodman et al, 1996;Singer et al, 1996Singer et al, , 1999Regan and Guo, 1997;Zaulyanov et al, 1999;, and mitochondrial toxins such as 3-nitropropionic acid (Wang et al, 2001a), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (De Girolamo et al, 2001, and sodium azide (Regan and Guo, 1997).…”

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confidence: 99%

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Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells

Wang

Dykens²,

Perez

et al. 2006

Molecular Pharmacology

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Neuroprotective effects of estrogens have been shown in various in vitro and in vivo models, but the mechanisms underlying protection by estrogen are not clear. Mounting evidence suggests antioxidant effects contribute to the neuroprotective effects of estrogens. In the present study, we assessed the protective effects of estrogens against H 2 O 2 -induced toxicity in human neuroblastoma cells and the potential mechanisms involved in this protection. We demonstrate that 17␤-estradiol (17␤-E 2 ) increases cell survival against H 2 O 2 toxicity in human neuroblastoma cells. 17␤-E 2 effectively reduced lipid peroxidation induced by 5-min H 2 O 2 exposure. Furthermore, 17␤-E 2 exerts the protective effects by maintaining intracellular Ca 2ϩ homeostasis, attenuating ATP depletion, ablating mitochondrial calcium overloading, and preserving mitochondrial membrane potential. Two nonfeminizing estrogens, 17␣-and entestradiol, were as effective as 17␤-E 2 in increasing cell survival, alleviating lipid peroxidation, preserving mitochondrial function, and maintaining intracellular glutathione levels and Ca 2ϩ homeostasis against H 2 O 2 insult. Moreover, the estrogen receptor antagonist fulvestrant (ICI 182,780) did not block effects of 17␤-E 2 , but increased cell survival and blunted intracellular Ca 2ϩ increases. However, these estrogens failed to reduce cytosolic reactive oxygen species, even at concentrations as high as 10 M. In conclusion, estrogens exert protective effects against oxidative stress by inhibiting lipid peroxidation and subsequently preserving Ca 2ϩ homeostasis, mitochondrial membrane potential, and ATP levels.In addition to their well established role as female sex hormones, estrogens have been shown to serve as neurotrophic and neuroprotective agents. Epidemiological studies show that early estrogen therapy can reduce the risk of neurodegenerative diseases such as Alzheimer's disease and improve cognition and memory in AD patients (Henderson et al

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Section: Estrogens and Mitochondrial Functionmentioning

confidence: 99%

mentioning

confidence: 99%

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells

Wang

Dykens²,

Perez

et al. 2006

Molecular Pharmacology

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“…It is likely that these protective actions involve a number of other actions of estrogens besides inducing synapses. These include suppression of the production of the toxic form of ␤-amyloid protein (59,153) and inhibition of free radical-induced toxicity (10,48). It should also be noted that estrogens affect many regions of the brain, including the basal forebrain cholinergic systems, the serotonergic system, the dopaminergic system, and the noradrenergic system [for review, see (93,94)], so that the hippocampus is not the only target that may be involved in these cognitive changes.…”

Section: Importance Of Sex Differences and Sex Hormonesmentioning

confidence: 99%

“…Some initial results indicate that diabetes may accelerate stress-induced dendritic atrophy in the hippocampus and promote stress-induced neuronal damage (84,121). A third approach is to use hippocampal cell culture models and study the interaction of androgens, estrogens, glucocorticoids, and excitatory amino acids in producing excitotoxic damage (48,116,117,126). As noted above, the vulnerability to excitotoxicity in hippocampal neurons has been related to increased calcium channel activity that develops with increasing age in culture (116).…”

Section: How To Define Protective Factors In the Brainmentioning

confidence: 99%

Stress and the Aging Hippocampus

McEwen

1999

Frontiers in Neuroendocrinology

208

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The ''glucocorticoid cascade hypothesis'' of hippocampal aging has stimulated a great deal of research into the neuroendocrine aspects of aging and the role of glucocorticoids, in particular. Besides strengthening the methods for investigating the aging brain, this research has revealed that the interactions between glucocorticoids and hippocampal neurons are far more complicated than originally envisioned and involve the participation of neurotransmitter systems, particularly the excitatory amino acids, as well as calcium ions and neurotrophins. New information has provided insights into the role of early experience in determining individual differences in brain and body aging by setting the reactivity of the hypothalamopituitary-adrenal axis and the autonomic nervous system. As a result of this research and advances in neuroscience and the study of aging, we now have a far more sophisticated view of the interactions among genes, early development, and environmental influences, as well as a greater appreciation of events at the cellular and molecular levels which protect neurons, and a greater appreciation of pathways of neuronal damage and destruction. While documenting the ultimate vulnerability of the brain to stressful challenges and to the aging process, the net result of this research has highlighted the resilience of the brain and offered new hope for treatment strategies for promoting the health of the aging brain. KEY WORDS: stress; hippocampal aging; glucocorticoid cascade hypothesis. 1999 Academic Press INTRODUCTIONThe hippocampus is a particularly vulnerable and sensitive region of the brain that is also very important for declarative and spatial learning and memory (36). Hippocampal neurons are vulnerable to seizures, strokes, and head trauma, as well as responding to stressful experiences (27,92,130). At the same time they show remarkable plasticity, involving long-term synaptic potentiation and depression, dendritic remodeling, synaptic turnover, and neurogenesis in the case of the dentate gyrus (Fig 1) (17,27,92).The work of aus der Muhlen and Ockenfels (3) first drew attention to potentially toxic actions of adrenal steroids. The reported darkly stained neurons in the hippocampus of guinea pigs exposed to high levels of glucocorticoids, an observation that has been confirmed and extended to repeated stress in subsequent studies (41,100), although there are still some doubts as to whether ''dark neurons'' may be artifacts of tissue trauma (18). In 1968, we discovered receptors for adrenal steroids in hippocampus (95), and it is now known that two types of adrenal steroid receptors exist in the hippocampus and other brain regions and mediate a variety of adrenal steroid effects on excitability, neurochemistry, and structure (27). Landfield (68) and then Sapolsky (127,128) provided evidence for a role of adrenal steroids in neuronal aging in the hippocampus, leading to the formulation of the ''glucocorticoid cascade hypothesis '' (130). This hypothesis states that glucocorticoids participate in a ...

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“…The pathological mechanisms that are activated during neurodegenerative diseases, including oxidative stress, excitotoxicity, inflammatory responses, mitochondrial dysfunction, and apoptosis, are antagonized by estrogens (Green et al, 1996(Green et al, , 1997a(Green et al, ,b, 1998Gridley et al, 1997). In vitro studies indicate that estrogens increase the viability and differentiation of primary cultures from different neuronal populations from the hypothalamus, amygdala, neocortex, or hippocampus.…”

Section: Introductionmentioning

confidence: 99%

Role of Protein Phosphatases in Estrogen-Mediated Neuroprotection

Yi¹,

Chung²,

Pang³

et al. 2005

J. Neurosci.

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The signaling pathways that mediate neurodegeneration are complex and involve a balance between phosphorylation and dephosphorylation of signaling and structural proteins. We have shown previously that 17␤-estradiol and its analogs are potent neuroprotectants. The purpose of this study was to delineate the role of protein phosphatases (PPs) in estrogen neuroprotection against oxidative stress and excitotoxicity. HT-22 cells, C6-glioma cells, and primary rat cortical neurons were exposed to the nonspecific serine/threonine protein phosphatase inhibitors okadaic acid and calyculin A at various concentrations in the presence or absence of 17␤-estradiol and/or glutamate. Okadaic acid and calyculin A caused a dose-dependent decrease in cell viability in HT-22, C6-glioma, and primary rat cortical neurons. 17␤-Estradiol did not show protection against neurotoxic concentrations of either okadaic acid or calyculin A in these cells. In the absence of these serine/threonine protein phosphatase inhibitors, 17␤-estradiol attenuated glutamate toxicity. However, in the presence of effective concentrations of these protein phosphatase inhibitors, 17␤-estradiol protection against glutamate toxicity was lost. Furthermore, glutamate treatment in HT-22 cells and primary rat cortical neurons caused a 50% decrease in levels of PP1, PP2A, and PP2B protein, whereas coadministration of 17␤-estradiol with glutamate prevented the decrease in PP1, PP2A, and PP2B levels. These results suggest that 17␤-estradiol may protect cells against glutamate-induced oxidative stress and excitotoxicity by activating a combination of protein phosphatases.

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Low concentrations of estradiol reduce β-amyloid (25–35)-induced toxicity, lipid peroxidation and glucose utilization in human SK-N-SH neuroblastoma cells

Cited by 122 publications

References 42 publications

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H2O2 Toxicity in Human Neuroblastoma SK-N-SH Cells

Stress and the Aging Hippocampus

Role of Protein Phosphatases in Estrogen-Mediated Neuroprotection

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