Biotin supply affects rates of cell proliferation, biotinylation of carboxylases and histones, and expression of the gene encoding the sodium-dependent multivitamin transporter in JAr choriocarcinoma cells

Sarah E.R.H. Crisp, Jacob B. Griffin, Brett R. White, Candice F. Toombs, Gabriela Camporeale, Hamid M. Said, Janos Zempleni

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Background: Placental transfer of nutrients and secretion of hormones is essential for normal fetal development. Aim of the study: To determine whether biotin supply affects biotin homeostasis, proliferation rates, and progesterone secretion in placenta cells. Methods: JAr choriocarcinoma cells were cultured in media containing deficient (25 pmol/L), physiological (250 pmol/L), or pharmacological concentrations (10,000 pmol/L) of biotin for three weeks; markers for biotin homeostasis, proliferation, and hormone secretion were quantified. Results: Biotin concentrations in culture media correlated negatively with expression of the biotin transporter SMVT, as judged by cellular transport rates of biotin, abundance of SMVT protein, and transcriptional activity of SMVT reporter-gene constructs. Notwithstanding this homeostatic mechanism, biotin concentrations in media correlated positively with activities of biotin-dependent propionyl-CoA carboxylase, abundance of biotinylated carboxylases, and with biotinylation of histones. Biotin deficiency was associated with decreased rates of thymidine uptake into JAr cells [pmol thymidine/(106 cells × 24h)]: 1.6 ± 0.1 (25 pmol/L biotin) versus 2.3 ± 0.2 (250 pmol/L biotin) versus 3.7 ± 0.4 (10,000 pmol/L biotin), suggesting that cell proliferation depends on biotin. Secretion of progesterone was reduced in biotin-deficient cells; this effect was caused by reduced generation of new cells in deficient media rather than by an immediate effect of biotin on progesterone secretion at the single-cell-level. Conclusions: This study provides evidence that choriocarcinoma cells cannot maintain normal activities of biotin-dependent metabolic pathways if biotin concentrations in culture media are low. It is uncertain whether activities of biotin-dependent pathways in placenta affect fetal development in vivo.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalEuropean Journal of Nutrition
Volume43
Issue number1
DOIs
StatePublished - Feb 2004

Keywords

  • Biotin
  • Carboxylases
  • Histones
  • Human
  • JAr cells
  • Placenta
  • Sodium-dependent multivitamin transporter

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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