Estrogen protection in Friedreich's ataxia skin fibroblasts

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Estrogens have been shown to have protective effects on a wide range of cell types and animal models for many neurodegenerative diseases. The present study demonstrates the cytoprotective effects of 17β-estradiol (E2) and estrogen-like compounds in an in vitro model of Friedreich's ataxia (FRDA) using human donor FRDA skin fibroblasts. FRDA fibroblasts are extremely sensitive to free radical damage and oxidative stress, produced here using L-buthionine (S,R)-sulfoximine to inhibit de novo glutathione synthesis. We have shown that the protective effect of E2 in the face of L-buthionine (S,R)-sulfoximine -induced oxidative stress is independent of estrogen receptor-α, estrogen receptor-β orGprotein-coupled receptor 30 as shown by the inability of either ICI 182,780 or G15 to inhibit the E2-mediated protection. These cytoprotective effects appear to be dependent on antioxidant properties and the phenolic structure of estradiol as demonstrated by the observation that all phenolic compounds tested were protective, whereas all nonphenolic compounds were inactive, and the observation that the phenolic compounds reduced the levels of reactive oxygen species, whereas the nonphenolic compounds did not. These data show for the first time that phenolic E2-like compounds are potent protectors against oxidative stress-induced cell death in FRDA fibroblasts and are possible candidate drugs for the treatment and prevention of FRDA symptoms.

Original languageEnglish
Pages (from-to)2742-2749
Number of pages8
JournalEndocrinology
Volume152
Issue number7
DOIs
StatePublished - 1 Jul 2011

Fingerprint

Friedreich Ataxia
Estrogens
Fibroblasts
Skin
Oxidative Stress
Estrogen Receptors
Estradiol
Neurodegenerative Diseases
Free Radicals
Glutathione
Reactive Oxygen Species
Cell Death
Animal Models
Antioxidants
Pharmaceutical Preparations

Cite this

Richardson, Timothy E. ; Yang, Shao Hua ; Wen, Yi ; Simpkins, James W. / Estrogen protection in Friedreich's ataxia skin fibroblasts. In: Endocrinology. 2011 ; Vol. 152, No. 7. pp. 2742-2749.
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Richardson, TE, Yang, SH, Wen, Y & Simpkins, JW 2011, 'Estrogen protection in Friedreich's ataxia skin fibroblasts', Endocrinology, vol. 152, no. 7, pp. 2742-2749. https://doi.org/10.1210/en.2011-0184

Estrogen protection in Friedreich's ataxia skin fibroblasts. / Richardson, Timothy E.; Yang, Shao Hua; Wen, Yi; Simpkins, James W.

In: Endocrinology, Vol. 152, No. 7, 01.07.2011, p. 2742-2749.

Research output: Contribution to journalArticle

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