论文部分内容阅读
Estrogen exerts a novel protective effect on cerebrovascular mitochondria by increasing levels of mitochondrial proteins important for energy production and free radical suppression.Treatment of ovariectomized rats with E affected key transcriptional coactivators responsible for regulating mitochondrial function and oxidative metabolism in cerebral blood vessels : lowering PGC-1 mRNA but increasing levels of other PGC-1 isoforms : PGC-1β and PGC1 related coactivator (PRC).Suppression of PGC-1 depended on receptormediated phosphatidylinositol 3-kinase (PI3K).In contrast, enhancement by E of nuclear respiratory factor 1 (NRF-1), a known PGC target and key factor in mitochondrial biogenesis, was independent of PI3K.E also increased cerebrovascular protein levels of mitochondrial transcription factor A and mitochondrial electron transport chain complex subunits as well as mitochondrial/nuclear DNA ratios.Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme for glutathione synthesis and downstream target of PGC-1β; E increased GCL subunit protein levels and total glutathione.Thus E differentially regulates PGC-1 isoforms in brain vasculature, underscoring unique mechanisms for adapting mitochondria to the needs of specific tissues.By upregulating PGC-1β and/or PRC, E enhances mitochondrial function, biogenesis and ROS protection in cerebral blood vessels.