Scavestrogens Protect IMR 32 Cells from Oxidative Stress-Induced Cell Death

Blum‐Degen, D.; Haas, Markus; Pohli, S.; Harth, R.; Römer, Wolfgang; Oettel, M; Riederer, Peter; Götz, Mario E.

doi:10.1006/taap.1998.8503

Cited by 35 publications

(23 citation statements)

References 37 publications

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“…Thus, we investigated the effect of E 2 , a well-known neurotrophic and neuroprotective hormone [52][53][54][55][56][57][63][64][65][66] , on Ngb expression. Our results indicated that E 2 increases Ngb levels of about 300% in both the human neuroblastoma cell line and mouse primary hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, estrogen therapy in post-menopausal women is associated with decreased incidence and enhanced recovery from ischemic stroke [51] . The protective effects of estrogens have been widely reported in different types of neuronal cells against a variety of insults, including H 2 O 2 [53,54] , serum deprivation [55] , oxygen-glucose deprivation [56] , and iron [57] . Due to myriad and often tissue-specific estrogen effects, the precise molecular events that mediate these protective actions are not fully understood.…”

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confidence: 99%

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17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H2O2-Induced Toxicity

Marinis¹,

Ascenzi²,

Pellegrini³

et al. 2010

Neurosignals

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Although discovered in 2000, neuroglobin (Ngb) functions are still uncertain. A contribution to the role played by Ngb in neurons could certainly derive from the identification of Ngb endogenous modulators. Here, we evaluate the possibility that Ngb could be regulated by 17β-estradiol (E₂) signaling in both SK-N-BE human neuroblastoma cell line and mouse hippocampal neurons. 1 nM E₂ rapidly induced a 300% increase in Ngb levels in both models. The E₂ effect was specific, being not induced by testosterone or dihydrotestosterone. The E₂-induced Ngb increase requires estrogen receptor (ER) β, but not ERα, as evaluated by the mimetic effect of ERβ-specific agonist DPN and by the blockage of E₂ effect in ERβ-silenced SK-N-BE cells. Furthermore, both rapid (15 min) ERβ-dependent activation of p38/MAPK and transcriptional ERβ activity were required for the estrogenic regulation of Ngb. Finally, E₂ exerted a protective effect against H₂O₂-induced neuroblastoma cell death which was completely prevented in Ngb-silenced cells. Overall, these data suggest that Ngb is part of the E₂ signaling mechanism that is activated to exert protective effects against H₂O₂-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H2O2-Induced Toxicity

Marinis¹,

Ascenzi²,

Pellegrini³

et al. 2010

Neurosignals

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“…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).…”

mentioning

confidence: 99%

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H₂O₂Toxicity in Human Neuroblastoma SK-N-SH Cells

Wang

Dykens²,

Perez

et al. 2006

Mol Pharmacol

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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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“…In contrast, the so-called scavestrogens J811 and J861, structurally derived from 17o~-estradiol, are blood-brain permeable. In vitro, these compounds are potent radical scavengers and inhibitors of iron-induced cell damage (R6mer et al, 1997) and can protect cultured IMR 32 neuroblastoma cells against Fenton reagent-mediated cell death (Blum-Degen et al, 1998). These results suggest that such compounds may be useful in the development of novel treatments for stroke and neurodegenerative disorders.…”

Section: Antioxidants Iron Chelators and Nos Inhibitorsmentioning

confidence: 87%

Strategies for the protection of dopaminergic neurons against neurotoxicity

et al. 2000

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Degenerative diseases of the central nervous system (CNS) frequently have a predilection for specific cell populations. An explanation for the selective vulnerability of particular neuronal populations and the mechanisms of cell death remains, as yet, elusive. Partial elucidation of the processes underlying the selective action of neurotoxic substances such as iron, 6-hydroxydopamine (6-OHDA), glutamate, kainic acid, quinolinic acid or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has revealed possible molecular mechanisms for neurodegeneration. Hypotheses regarding the neurotoxic mechanisms of these substances have evolved based on our understanding of the pathogenesis of cell death in neurodegenerative disorders and have been the rationale for neuroprotective approaches. Various experimental models have demonstrated that monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists exert a neuroprotective effect at the cellular, neurochemical and functional levels, however as yet it has not been possible to demonstrate an unequivocal neuroprotective effect of these substances in clinical studies. This does not suggest, however, that the pathogenetic processes underlying neurodegenerative disorders are not amenable to neuroprotective treatment. This chapter briefly reviews the mechanisms underlying dopaminergic cell death in Parkinson's disease (PD) as an example of a neurodegenerative disorder and discusses preclinical approaches which attempt to demonstrate the neuroprotective effects of representative drugs in experimental models of this disorder. The problems associated with carrying out clinical neuroprotective studies aimed to demonstrate neuroprotection in PD are also discussed.

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Scavestrogens Protect IMR 32 Cells from Oxidative Stress-Induced Cell Death

Cited by 35 publications

References 37 publications

17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H<sub>2</sub>O<sub>2</sub>-Induced Toxicity

17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H<sub>2</sub>O<sub>2</sub>-Induced Toxicity

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H₂O₂Toxicity in Human Neuroblastoma SK-N-SH Cells

Strategies for the protection of dopaminergic neurons against neurotoxicity

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Scavestrogens Protect IMR 32 Cells from Oxidative Stress-Induced Cell Death

Cited by 35 publications

References 37 publications

17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H<sub>2</sub>O<sub>2</sub>-Induced Toxicity

17β-Estradiol – A New Modulator of Neuroglobin Levels in Neurons: Role in Neuroprotection against H<sub>2</sub>O<sub>2</sub>-Induced Toxicity

Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H2O2Toxicity in Human Neuroblastoma SK-N-SH Cells

Strategies for the protection of dopaminergic neurons against neurotoxicity

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Neuroprotective Effects of 17β-Estradiol and Nonfeminizing Estrogens against H₂O₂Toxicity in Human Neuroblastoma SK-N-SH Cells