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Felty, Quentin; Roy, Deodutta

doi:10.1186/1477-3163-4-1

Cited by 91 publications

(29 citation statements)

References 173 publications

(171 reference statements)

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“…Despite the fact that many of the mitochondrial effects of estrogens appear to be modulated by non-nuclear ERs [88, 89], research to date has focused on hormone analogs and other compounds that act primarily via the classical nuclear ERs. Future experiments will be needed to investigate the specific role of membrane estrogen receptors (including GqMER) in transducing the protective effects of STX on mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

Gray

Zweig

Kawamoto

et al. 2016

JAD

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Because STX is a selective ligand for membrane estrogen receptors, it may be able to confer the beneficial effects of estrogen without eliciting the deleterious side effects associated with activation of the nuclear estrogen receptors. This study evaluates the neuroprotective properties of STX in the context of amyloid-β (Aβ) exposure. MC65 and SH-SY5Y neuroblastoma cell lines, as well as primary hippocampal neurons from wild type (WT) and Tg2576 mice, were used to investigate the ability of STX to attenuate cell death, mitochondrial dysfunction, dendritic simplification, and synaptic loss induced by Aβ. STX prevented Aβ-induced cell death in both neuroblastoma cell lines; it also normalized the decrease in ATP and mitochondrial gene expression caused by Aβ in these cells. Notably, STX also increased ATP content and mitochondrial gene expression in control neuroblastoma cells (in the absence of Aβ). Likewise in primary neurons, STX increased ATP levels and mitochondrial gene expression in both genotypes. In addition, STX treatment enhanced dendritic arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites caused by Aβ exposure in Tg2576 neurons. These data suggest that STX can act as an effective neuroprotective agent in the context of Aβ toxicity, improving mitochondrial function as well as dendritic growth and synaptic differentiation. In addition, since STX also improved these endpoints in the absence of Aβ, this compound may have broader therapeutic value beyond Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

Gray

Zweig

Kawamoto

et al. 2016

JAD

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“…T. Wang & Phang, 1995; Yamamoto et al, 2014). For instance, ER induced changes in mitochondrial dynamics, oxidative stress, and DNA damage have been shown to increase proliferation of ER+ breast cancer epithelial cells (Caldon, 2014; Felty & Roy, 2005; Felty, Singh, & Roy, 2005). Modulation of mitochondrial dynamics, proliferation and oxidative stress increase DNA damage, which can lead to pro-cancerous mutations (Caldon, 2014; Mobley & Brueggemeier, 2004; Sastre-Serra, et al, 2010).…”

Section: The Therapeutic Outcome Pathway: a Conceptual Framework Tmentioning

confidence: 99%

Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement

Morgan

Johnson

Livingston

et al. 2016

Pharmacology & Therapeutics

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Personalized cancer therapy focuses on characterizing the relevant phenotypes of the patient, as well as the patient’s tumor, to predict the most effective cancer therapy. Historically, these methods have not proven predictive in regards to predicting therapeutic response. Emerging culture platforms are designed to better recapitulate the in vivo environment, thus, there is renewed interest in integrating patient samples into in vitro cancer models to assess therapeutic response. Successful examples of translating in vitro response to clinical relevance are limited due to issues with patient sample acquisition, variability and culture. We will review traditional and emerging in vitro models for personalized medicine, focusing on the technologies, microenvironmental components, and readouts utilized. We will then offer our perspective on how to apply a framework derived from toxicology and ecology towards designing improved personalized in vitro models of cancer. The framework serves as a tool for identifying optimal readouts and culture conditions, thus maximizing the information gained from each patient sample.

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“…There is accumulating evidence suggesting that mitochondria are also important targets for the actions of estrogens (18,27). Mitochondria play a fundamental role in cellular respiration, oxidative phosphorylation, and ionic homeostasis as well as synthesis of heme, lipids, amino acids, and nucleotide.…”

mentioning

confidence: 99%

“…Mitochondria play a fundamental role in cellular respiration, oxidative phosphorylation, and ionic homeostasis as well as synthesis of heme, lipids, amino acids, and nucleotide. Not only is endogenous estrogen synthesized in the mitochondria by aromatase, but exogenously added estrogen is also mainly transported into this organelle (27,28). We and several other laboratories have recently reported the localization of ER␤ in mitochondria in various cells, including rat primary neurons (15,18,29), rat primary cardiomyocytes (15), a murine hippocampal cell line (HT-22), neurons and glia in rat hippocampus (13,14), human breast cancer cell lines (MCF-7 and MCF-10F) (16,18), immortal human breast epithelial cells (18), human lens epithelial cell lines (nHLE and HLE-B3) (17,30), human osteosarcoma cells (SaOS-2) (31), hepatocarcinoma cells (HepG2) (31), and human sperm (32).…”

mentioning

confidence: 99%

Estrogen Receptor β as a Mitochondrial Vulnerability Factor

Yang

Sarkar

Liu

et al. 2009

Journal of Biological Chemistry

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We recently demonstrated mitochondrial localization of estrogen receptor ␤ (ER␤). We herein confirm the mitochondrial localization of ER␤ by the loss of mitochondrial ER␤ immunoreactivity in ER␤ knockdown cells. A phenotype change characterized as an increase in resistance to oxidative stressors is associated with ER␤ knockdown. ER␤ knockdown results in a lower resting mitochondrial membrane potential (⌬m) and increase in resistance to hydrogen peroxide-induced ⌬m depolarization in both immortal hippocampal cells and primary hippocampal neurons. ER␤ knockdown cells maintained ATP concentrations despite insults that compromise ATP production and produce less mitochondrial superoxide under oxidative stress. Furthermore, similar mitochondrial phenotype changes were identified in primary hippocampal neurons derived from ER␤ knock-out mice. These data demonstrate that ER␤ is expressed in mitochondria and function as a mitochondrial vulnerability factor involved in ⌬m maintenance, potentially through a mitochondrial transcription dependent mechanism.

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Untitled

Cited by 91 publications

References 173 publications

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement

Estrogen Receptor β as a Mitochondrial Vulnerability Factor

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