Mitochondrial translocation of estrogen receptor β affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis

Tien Ling Liao, Yu Ching Lee, Chii Ruey Tzeng, Yi Pei Wang, Heng Yu Chang, Yung Feng Lin, Shu Huei Kao

研究成果: 雜誌貢獻文章

1 引文 (Scopus)

摘要

Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.
原文英語
頁(從 - 到)359-373
頁數15
期刊Free Radical Biology and Medicine
134
DOIs
出版狀態已發佈 - 四月 1 2019

指紋

Endometriosis
Estrogen Receptors
Apoptosis
Mitochondria
Mitochondrial DNA
Energy Metabolism
Estradiol
Reactive Oxygen Species
Tissue
Female Infertility
Selective Estrogen Receptor Modulators
Oligomycins
Choristoma
Apoptosis Regulatory Proteins
Mitochondrial Genes
Cytoprotection
Gene expression
Restoration
Superoxide Dismutase
Estrogens

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

引用此文

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title = "Mitochondrial translocation of estrogen receptor β affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis",
abstract = "Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.",
keywords = "Anti-apoptosis, Cell migration, Endometriosis, Mitochondrial bioenergetics, Mitochondrial estrogen receptor β, Oxidative stress",
author = "Liao, {Tien Ling} and Lee, {Yu Ching} and Tzeng, {Chii Ruey} and Wang, {Yi Pei} and Chang, {Heng Yu} and Lin, {Yung Feng} and Kao, {Shu Huei}",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.freeradbiomed.2019.01.022",
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pages = "359--373",
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T1 - Mitochondrial translocation of estrogen receptor β affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis

AU - Liao, Tien Ling

AU - Lee, Yu Ching

AU - Tzeng, Chii Ruey

AU - Wang, Yi Pei

AU - Chang, Heng Yu

AU - Lin, Yung Feng

AU - Kao, Shu Huei

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.

AB - Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.

KW - Anti-apoptosis

KW - Cell migration

KW - Endometriosis

KW - Mitochondrial bioenergetics

KW - Mitochondrial estrogen receptor β

KW - Oxidative stress

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