ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: Relevance to pathomechanisms of pseudoxanthoma elasticum

Krisztina Fülöp, Qiujie Jiang, Koen v.d. Wetering, Viola Pomozi, Pál T. Szabó, Tamás Arányi, Balázs Sarkadi, Piet Borst, Jouni Uitto, András Váradi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6 -/- mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6 -/- animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum.

Original languageEnglish
Pages (from-to)468-471
Number of pages4
JournalBiochemical and biophysical research communications
Volume415
Issue number3
DOIs
Publication statusPublished - Nov 25 2011

Keywords

  • Conjugate transport
  • Liver perfusion
  • Pseudoxanthoma elasticum
  • Soft tissue calcification
  • Vitamin K metabolism

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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