Estrogen-mediated neuroprotection against β-amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway

Jennifer L. Fitzpatrick, Amy L. Mize, Christian B. Wade, Julie A. Harris, Robert A. Shapiro, Daniel Dorsa

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non-classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) α and/or β to mediate such responses is lacking, the hippocampal-derived cell line HT22 was stably transfected with either ERα (HTERα) or ERβ (HTERβ). In HTERα and HTERβ cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17β-estradiol treatment. The ER antagonist ICI 182, 780 (1 μM) and the MEK inhibitor, PD98059 (50 μM) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERα and HTERβ cells with the β-amyloid peptide (25-35) (10 μM) resulted in a significant decrease in cell viability. Pre-treatment 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. Finally, ICI 182, 780 and PD98059 prevented 17β-estradiol-mediated protection. This study demonstrates that both ERα and ERβ can couple to rapid signaling events that mediate estrogen-elicited neuroprotection.

Original languageEnglish (US)
Pages (from-to)674-682
Number of pages9
JournalJournal of Neurochemistry
Volume82
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Amyloid
Estrogen Receptors
Toxicity
Estrogens
Chemical activation
Cells
Estradiol
Phosphorylation
Cell Survival
Mitogen-Activated Protein Kinase Kinases
Neuroprotection
Cell Count
Peptides
Cell Line
fulvestrant
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Keywords

  • β-amyloid
  • ERK2
  • Estrogen
  • Estrogen receptor
  • HT22
  • Neuroprotection

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Estrogen-mediated neuroprotection against β-amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway. / Fitzpatrick, Jennifer L.; Mize, Amy L.; Wade, Christian B.; Harris, Julie A.; Shapiro, Robert A.; Dorsa, Daniel.

In: Journal of Neurochemistry, Vol. 82, No. 3, 2002, p. 674-682.

Research output: Contribution to journalArticle

Fitzpatrick, Jennifer L. ; Mize, Amy L. ; Wade, Christian B. ; Harris, Julie A. ; Shapiro, Robert A. ; Dorsa, Daniel. / Estrogen-mediated neuroprotection against β-amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway. In: Journal of Neurochemistry. 2002 ; Vol. 82, No. 3. pp. 674-682.
@article{dad687c4076c4475a5910b49f2f873cc,
title = "Estrogen-mediated neuroprotection against β-amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway",
abstract = "It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non-classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) α and/or β to mediate such responses is lacking, the hippocampal-derived cell line HT22 was stably transfected with either ERα (HTERα) or ERβ (HTERβ). In HTERα and HTERβ cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17β-estradiol treatment. The ER antagonist ICI 182, 780 (1 μM) and the MEK inhibitor, PD98059 (50 μM) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERα and HTERβ cells with the β-amyloid peptide (25-35) (10 μM) resulted in a significant decrease in cell viability. Pre-treatment 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. Finally, ICI 182, 780 and PD98059 prevented 17β-estradiol-mediated protection. This study demonstrates that both ERα and ERβ can couple to rapid signaling events that mediate estrogen-elicited neuroprotection.",
keywords = "β-amyloid, ERK2, Estrogen, Estrogen receptor, HT22, Neuroprotection",
author = "Fitzpatrick, {Jennifer L.} and Mize, {Amy L.} and Wade, {Christian B.} and Harris, {Julie A.} and Shapiro, {Robert A.} and Daniel Dorsa",
year = "2002",
doi = "10.1046/j.1471-4159.2002.01000.x",
language = "English (US)",
volume = "82",
pages = "674--682",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Estrogen-mediated neuroprotection against β-amyloid toxicity requires expression of estrogen receptor α or β and activation of the MAPK pathway

AU - Fitzpatrick, Jennifer L.

AU - Mize, Amy L.

AU - Wade, Christian B.

AU - Harris, Julie A.

AU - Shapiro, Robert A.

AU - Dorsa, Daniel

PY - 2002

Y1 - 2002

N2 - It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non-classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) α and/or β to mediate such responses is lacking, the hippocampal-derived cell line HT22 was stably transfected with either ERα (HTERα) or ERβ (HTERβ). In HTERα and HTERβ cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17β-estradiol treatment. The ER antagonist ICI 182, 780 (1 μM) and the MEK inhibitor, PD98059 (50 μM) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERα and HTERβ cells with the β-amyloid peptide (25-35) (10 μM) resulted in a significant decrease in cell viability. Pre-treatment 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. Finally, ICI 182, 780 and PD98059 prevented 17β-estradiol-mediated protection. This study demonstrates that both ERα and ERβ can couple to rapid signaling events that mediate estrogen-elicited neuroprotection.

AB - It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non-classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) α and/or β to mediate such responses is lacking, the hippocampal-derived cell line HT22 was stably transfected with either ERα (HTERα) or ERβ (HTERβ). In HTERα and HTERβ cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17β-estradiol treatment. The ER antagonist ICI 182, 780 (1 μM) and the MEK inhibitor, PD98059 (50 μM) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERα and HTERβ cells with the β-amyloid peptide (25-35) (10 μM) resulted in a significant decrease in cell viability. Pre-treatment 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. Finally, ICI 182, 780 and PD98059 prevented 17β-estradiol-mediated protection. This study demonstrates that both ERα and ERβ can couple to rapid signaling events that mediate estrogen-elicited neuroprotection.

KW - β-amyloid

KW - ERK2

KW - Estrogen

KW - Estrogen receptor

KW - HT22

KW - Neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=0036320770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036320770&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.2002.01000.x

DO - 10.1046/j.1471-4159.2002.01000.x

M3 - Article

C2 - 12153491

AN - SCOPUS:0036320770

VL - 82

SP - 674

EP - 682

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -