Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-activated protein kinase pathway

Amy L. Mize, Robert A. Shapiro, Daniel Dorsa

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

It is well documented that estrogen mediates responses by both genomic and nongenomic mechanisms, both of which are important for cell survival. Because direct evidence showing that the estrogen receptors (ERs) α and/or β can activate rapid signaling that may mediate neuroprotection is lacking, the hippocampal-derived cell line, HT22, was stably transfected with ERα (HTERα), ERβ (HTERβ), or a mutated form of ERα (HTERαHE27), which lacks the ability to mediate ER element-mediated transcription. Treatment of HT22, HTERα, HTERβ, and HTERαHE27 cells with glutamate (5 mM) resulted in a significant decrease in cell viability. Pretreatment for 15 min with 10 nM 17β-estradiol resulted in a 50% increase in the number of living cells in HTERα and HTERβ cells but not in HT22 cells. The ER antagonist ICI 182,780 and the MEK inhibitor PD98059 prevented 17β-estradiol-mediated protection. In HTERαHE27 cells, 17β-estradiol rapidly phosphorylated ERK2 (within 15 min), in the absence of estrogen response element-mediated transcription. Treatment of HTERαHE27 cells with 10 nM 17β-estradiol partially reversed the cell death produced by glutamate treatment. This study demonstrates that activation of either ERα or ERβ can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.

Original languageEnglish (US)
Pages (from-to)306-312
Number of pages7
JournalEndocrinology
Volume144
Issue number1
DOIs
StatePublished - Jan 1 2003

Fingerprint

Mitogen-Activated Protein Kinases
Estrogen Receptors
Oxidative Stress
Estradiol
Glutamic Acid
Cell Survival
Estrogens
Mitogen-Activated Protein Kinase Kinases
Response Elements
Neuroprotection
Cell Death
Cell Count
Cell Line

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-activated protein kinase pathway. / Mize, Amy L.; Shapiro, Robert A.; Dorsa, Daniel.

In: Endocrinology, Vol. 144, No. 1, 01.01.2003, p. 306-312.

Research output: Contribution to journalArticle

@article{9892674f1f524fdd9616f7a4cb056a94,
title = "Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-activated protein kinase pathway",
abstract = "It is well documented that estrogen mediates responses by both genomic and nongenomic mechanisms, both of which are important for cell survival. Because direct evidence showing that the estrogen receptors (ERs) α and/or β can activate rapid signaling that may mediate neuroprotection is lacking, the hippocampal-derived cell line, HT22, was stably transfected with ERα (HTERα), ERβ (HTERβ), or a mutated form of ERα (HTERαHE27), which lacks the ability to mediate ER element-mediated transcription. Treatment of HT22, HTERα, HTERβ, and HTERαHE27 cells with glutamate (5 mM) resulted in a significant decrease in cell viability. Pretreatment for 15 min with 10 nM 17β-estradiol resulted in a 50{\%} increase in the number of living cells in HTERα and HTERβ cells but not in HT22 cells. The ER antagonist ICI 182,780 and the MEK inhibitor PD98059 prevented 17β-estradiol-mediated protection. In HTERαHE27 cells, 17β-estradiol rapidly phosphorylated ERK2 (within 15 min), in the absence of estrogen response element-mediated transcription. Treatment of HTERαHE27 cells with 10 nM 17β-estradiol partially reversed the cell death produced by glutamate treatment. This study demonstrates that activation of either ERα or ERβ can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.",
author = "Mize, {Amy L.} and Shapiro, {Robert A.} and Daniel Dorsa",
year = "2003",
month = "1",
day = "1",
doi = "10.1210/en.2002-220698",
language = "English (US)",
volume = "144",
pages = "306--312",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Estrogen receptor-mediated neuroprotection from oxidative stress requires activation of the mitogen-activated protein kinase pathway

AU - Mize, Amy L.

AU - Shapiro, Robert A.

AU - Dorsa, Daniel

PY - 2003/1/1

Y1 - 2003/1/1

N2 - It is well documented that estrogen mediates responses by both genomic and nongenomic mechanisms, both of which are important for cell survival. Because direct evidence showing that the estrogen receptors (ERs) α and/or β can activate rapid signaling that may mediate neuroprotection is lacking, the hippocampal-derived cell line, HT22, was stably transfected with ERα (HTERα), ERβ (HTERβ), or a mutated form of ERα (HTERαHE27), which lacks the ability to mediate ER element-mediated transcription. Treatment of HT22, HTERα, HTERβ, and HTERαHE27 cells with glutamate (5 mM) resulted in a significant decrease in cell viability. Pretreatment for 15 min with 10 nM 17β-estradiol resulted in a 50% increase in the number of living cells in HTERα and HTERβ cells but not in HT22 cells. The ER antagonist ICI 182,780 and the MEK inhibitor PD98059 prevented 17β-estradiol-mediated protection. In HTERαHE27 cells, 17β-estradiol rapidly phosphorylated ERK2 (within 15 min), in the absence of estrogen response element-mediated transcription. Treatment of HTERαHE27 cells with 10 nM 17β-estradiol partially reversed the cell death produced by glutamate treatment. This study demonstrates that activation of either ERα or ERβ can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.

AB - It is well documented that estrogen mediates responses by both genomic and nongenomic mechanisms, both of which are important for cell survival. Because direct evidence showing that the estrogen receptors (ERs) α and/or β can activate rapid signaling that may mediate neuroprotection is lacking, the hippocampal-derived cell line, HT22, was stably transfected with ERα (HTERα), ERβ (HTERβ), or a mutated form of ERα (HTERαHE27), which lacks the ability to mediate ER element-mediated transcription. Treatment of HT22, HTERα, HTERβ, and HTERαHE27 cells with glutamate (5 mM) resulted in a significant decrease in cell viability. Pretreatment for 15 min with 10 nM 17β-estradiol resulted in a 50% increase in the number of living cells in HTERα and HTERβ cells but not in HT22 cells. The ER antagonist ICI 182,780 and the MEK inhibitor PD98059 prevented 17β-estradiol-mediated protection. In HTERαHE27 cells, 17β-estradiol rapidly phosphorylated ERK2 (within 15 min), in the absence of estrogen response element-mediated transcription. Treatment of HTERαHE27 cells with 10 nM 17β-estradiol partially reversed the cell death produced by glutamate treatment. This study demonstrates that activation of either ERα or ERβ can result in neuroprotection and that activation of the MAPK pathway is an important part of the neuroprotective mechanism.

UR - http://www.scopus.com/inward/record.url?scp=0037233177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037233177&partnerID=8YFLogxK

U2 - 10.1210/en.2002-220698

DO - 10.1210/en.2002-220698

M3 - Article

C2 - 12488359

AN - SCOPUS:0037233177

VL - 144

SP - 306

EP - 312

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 1

ER -