Vitamin K2 binds 17β-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism

Motoyuki Otsuka, Naoya Kato, Tohru Ichimura, Shinya Abe, Yasuo Tanaka, Hiroyoshi Taniguchi, Yujin Hoshida, Masaru Moriyama, Yue Wang, Run Xuan Shao, Dharel Narayan, Ryosuke Muroyama, Fumihiko Kanai, Takao Kawabe, Toshiaki Isobe, Masao Omata

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Vitamin K is a cofactor for γ-glutamyl carboxylase, an enzyme that is important for blood coagulation. Recent studies have shown that vitamin K has other roles, in addition to post-transcriptional modification, such as bone metabolism and antitumoral actions; these findings have indicated that there might be unknown intracellular binding proteins that are specific for vitamin K. In this study, vitamin K-binding proteins were characterized by pull-down experiment using a chemically synthesized biotynylated vitamin K followed by mass spectrometric identification of the pull-downed components. The results indicated that 17β hydroxy steroid dehydrogenase 4, apolipoportein E, and 40S ribosomal proteins S7 and S13 might be the candidates of the vitamin K-binding proteins. Subsequent experiments showed that vitamin K2 binds 17β hydroxysteroid dehydrogenase 4 and decreases the intracellular estradiol:estrone ratio, which resulted in the inhibition of the amount of estrogen receptor α-binding to its target DNA. These results suggest a possible novel role for vitamin K in modulating estrogen function.

Original languageEnglish (US)
Pages (from-to)2473-2482
Number of pages10
JournalLife Sciences
Volume76
Issue number21
DOIs
StatePublished - Apr 8 2005

Keywords

  • 17β-HSD4
  • Estrogen
  • Mass spectrometry
  • Vitamin K

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Otsuka, M., Kato, N., Ichimura, T., Abe, S., Tanaka, Y., Taniguchi, H., Hoshida, Y., Moriyama, M., Wang, Y., Shao, R. X., Narayan, D., Muroyama, R., Kanai, F., Kawabe, T., Isobe, T., & Omata, M. (2005). Vitamin K2 binds 17β-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism. Life Sciences, 76(21), 2473-2482. https://doi.org/10.1016/j.lfs.2004.12.020