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• W2033504349 endingPage "622" @default.
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• W2033504349 abstract "Estrogen has direct and indirect effects on mitochondrial activity, but the mechanisms mediating these effects remain unclear. Others reported that long-term estradiol (E(2)) treatment increased nuclear respiratory factor-1 (NRF-1) protein in cerebral blood vessels of ovariectomized rats. NRF-1 is a transcription factor that regulates the expression of nuclear-encoded mitochondrial genes, e.g. mitochondrial transcription factor A (TFAM), that control transcription of the mitochondrial genome. Here we tested the hypothesis that E(2) increases NRF-1 transcription resulting in a coordinate increase in the expression of nuclear- and mitochondrial- encoded genes and mitochondrial respiratory activity. We show that E(2) increased NRF-1 mRNA and protein in MCF-7 breast and H1793 lung adenocarcinoma cells in a time-dependent manner. E(2)-induced NRF-1 expression was inhibited by the estrogen receptor (ER) antagonist ICI 182,780 and actinomycin D but not by phosphoinositide-3 kinase and MAPK inhibitors, indicating a genomic mechanism of E(2) regulation of NRF-1 transcription. An estrogen response element (ERE) in the NRF-1 promoter bound ER alpha and ER beta in vitro, and E(2) induced ER alpha and ER beta recruitment to this ERE in chromatin immunoprecipitation assays in MCF-7 cells. The NRF-1 ERE activated reporter gene expression in transfected cells. Small interfering RNA to ER alpha and ER beta revealed that ER alpha mediates E(2)-induced NRF-1 transcription. The E(2)-induced increase in NRF-1 was followed by increased TFAM and the transcription of Tfam-regulated mitochondrial DNA-encoded COI and NDI genes and increased mitochondrial biogenesis. Knockdown of NRF-1 blocked E(2) stimulation of mitochondrial biogenesis and activity, indicating a mechanism by which estrogens regulate mitochondrial function by increasing NRF-1 expression." @default.
• W2033504349 created "2016-06-24" @default.
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• W2033504349 date "2008-03-01" @default.
• W2033504349 modified "2023-10-01" @default.
• W2033504349 title "Estradiol Stimulates Transcription of Nuclear Respiratory Factor-1 and Increases Mitochondrial Biogenesis" @default.
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• W2033504349 doi "https://doi.org/10.1210/me.2007-0029" @default.
• W2033504349 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2262171" @default.
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