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.
BACKGROUND
Placental transfer of nutrients and secretion of hormones is essential for normal fetal development.


OBJECTIVE
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/( 10(6) cells x 24 h)]: 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 singlecell-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.
Crisp
Sarah E R H
SE
Dept. of Nutritional Science and Dietetics, University of Nebraska at Lincoln, 316 Ruth Leverton Hall, Lincoln, NE 68583-0806, USA.
Griffin
Jacob B
JB
White
Brett R
BR
Toombs
Candice F
CF
Camporeale
Gabriela
G
Said
Hamid M
HM
Zempleni
Janos
J
D001710:Biotin / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology*; D043523:Biotinidase / Q000235:genetics / Q000378:metabolism; D019921:Biotinylation; D002262:Carboxy-Lyases / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002822:Choriocarcinoma; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D017930:Genes, Reporter; D006657:Histones / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D012256:Riboflavin / Q000378:metabolism; D027981:Symporters; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D003470:Culture Media; D006657:Histones; D008562:Membrane Glycoproteins; D027981:Symporters; C119981:biotin transporter; D001710:Biotin; D043523:Biotinidase; D002262:Carboxy-Lyases; D012256:Riboflavin