Estrogen prevents oxidative damage to the mitochondria in Friedreich's ataxia skin fibroblasts

Timothy E. Richardson, Amanda E. Yu, Yi Wen, Shao Hua Yang, James W. Simpkins

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Estrogen and estrogen-related compounds have been shown to have very potent cytoprotective properties in a wide range of disease models, including an in vitro model of Friedreich's ataxia (FRDA). This study describes a potential estrogen receptor (ER)-independent mechanism by which estrogens act to protect human FRDA skin fibroblasts from a BSO-induced oxidative insult resulting from inhibition of de novo glutathione (GSH) synthesis. We demonstrate that phenolic estrogens, independent of any known ER, are able to prevent lipid peroxidation and mitochondrial membrane potential (ΔΨm) collapse, maintain ATP at near control levels, increase oxidative phosphorylation and maintain activity of aconitase. Estrogens did not, however, prevent BSO from depleting GSH or induce an increased expression level of GSH. The cytoprotective effects of estrogen appear to be due to a direct overall reduction in oxidative damage to the mitochondria, enabling the FRDA fibroblast mitochondria to generate sufficient ATP for energy requirements and better survive oxidative stress. These data support the hypothesis that phenol ring containing estrogens are possible candidate drugs for the delay and/or prevention of FRDA symptoms.

Original languageEnglish
Article numbere34600
JournalPLoS ONE
Volume7
Issue number4
DOIs
StatePublished - 3 Apr 2012

Fingerprint

Friedreich Ataxia
Mitochondria
Fibroblasts
skin (animal)
estrogens
fibroblasts
Skin
Estrogens
mitochondria
Estrogen Receptors
Adenosine Triphosphate
Aconitate Hydratase
aconitate hydratase
Oxidative stress
oxidative phosphorylation
disease models
Mitochondrial Membrane Potential
Oxidative Phosphorylation
Level control
Phenol

Cite this

Richardson, Timothy E. ; Yu, Amanda E. ; Wen, Yi ; Yang, Shao Hua ; Simpkins, James W. / Estrogen prevents oxidative damage to the mitochondria in Friedreich's ataxia skin fibroblasts. In: PLoS ONE. 2012 ; Vol. 7, No. 4.
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Estrogen prevents oxidative damage to the mitochondria in Friedreich's ataxia skin fibroblasts. / Richardson, Timothy E.; Yu, Amanda E.; Wen, Yi; Yang, Shao Hua; Simpkins, James W.

In: PLoS ONE, Vol. 7, No. 4, e34600, 03.04.2012.

Research output: Contribution to journalArticle

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