Estrogen induces nitric oxide production via activation of constitutive nitric oxide synthases in human neuroblastoma cells

Endocrinology
Yun Xia, Teresa L Krukoff

Abstract

Although it is becoming increasingly evident that nitric oxide (NO) mediates some of estrogen's actions in the brain, the effects of estrogen on NO production through NO synthases (NOS) in neuronal cells have not yet been identified. Here we assessed changes in NO production induced by 17beta-estradiol (E2) in cells of neuronal origin using human SK-N-SH neuroblastoma cells, which we show express all three isoforms of NOS. Involvement of NOS isoforms in E2-induced NO production was examined using isoform-specific NOS inhibitors. E2 (10(-10)-10(-6) m) induced rapid increases in NO release and changes in endothelial NOS (eNOS) expression, which were blocked by ICI 182,780, an antagonist of estrogen receptors. Increased levels of NO release and NOS activity induced by E2 were blocked by N5-(1-Imino-3-butenyl)-L-ornithine, a neuronal NOS inhibitor, and N(5)-(1-Iminoethyl)-L-ornithine, an eNOS inhibitor, but not by 1400W, an inducible NOS inhibitor. These results demonstrate that E2-stimulated NO production occurs via estrogen receptor-mediated activation of the constitutive NOSs, neuronal NOS and eNOS. The E2-induced NO increase was abolished when extracellular Ca2+ was removed from the medium or after the addition of nifedipine, a...Continue Reading

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Citations

May 30, 2006·Nature Chemical Biology·Mi Hee LimStephen J Lippard
Apr 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lindsey E McQuadeStephen J Lippard
Apr 10, 2009·PloS One·Naohito KitamuraMasahisa Yamada
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May 6, 2021·International Journal of Molecular Sciences·Lalita SubediSun-Yeou Kim

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