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Estrogen Modulates Mitochondria‐dependent ROS Production in Human Brain Endothelial Cells
Author(s) -
Sunday Lorraine Nkeiru,
Procaccio Vincent,
Krause Dia,
Duckles Sue P
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb106-b
Subject(s) - mitochondrial ros , reactive oxygen species , mitochondrion , oxidative stress , estrogen , oxidative phosphorylation , microbiology and biotechnology , chemistry , biology , biochemistry , endocrinology
Oxidative stress is a common unifying mechanism for many cardiovascular disease risk factors, and mitochondria are a major producer of reactive oxygen species (ROS) as a by‐product of oxidative phosphorylation. However, results of using antioxidants to prevent cardiovascular disease have been conflicting, underscoring the need to understand the sources of ROS as well as factors that modulate ROS levels. We have recently shown that estrogen has profound effects on mitochondrial function in cerebral arteries, including increasing energy efficiency and decreasing mitochondrial ROS production. To further explore effects of estrogen we used human brain microvascular endothelial cells (HBMEC) treated with 10 nM estrogen or cyclodextrin vehicle for 48 hours prior to mitochondria isolation. Western blot analysis showed an increase in mitochondrial cytochrome c, which plays a dual role, increasing energy efficiency and acting as an antioxidant. We also measured ROS levels by two methods. Direct measurement of ROS in live cells using MitoSOX dye (Molecular Probes) showed that 10 nM estrogen significantly decreased mitochondrial ROS to 35 ± 6% of vehicle levels. Measurement of aconitase activity as a functional indicator of mitochondrial ROS showed that estrogen protected aconitase activity by 4 fold compared to vehicle. Thus estrogen increases mitochondrial cytochrome c and decreases mitochondrial ROS. Future studies will assess whether estrogen protects against mitochondrial DNA damage and explore in more depth the effect of estrogen on mitochondrial enzyme function. Supported by NIH RO1 HL‐50775.