Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells.
Biotin supply may affect transcription of genes and biotinylation of proteins in cells. In this study, Jurkat cells were used to model effects of biotin supply on biotin homeostasis and interleukin-2 metabolism in immune cells. Cells were cultured in media containing deficient (25 pmol/L), physiologic (250 pmol/L), or pharmacologic concentrations (10,000 pmol/L) of biotin for 4 wk. Activities of the biotin-dependent enzyme propionyl-CoA carboxylase paralleled the biotin concentrations in media [pmol bicarbonate fixed/(min x 10(6) cells)]: 1.9 +/- 0.7 (25 pmol/L biotin) vs. 19 +/- 1.2 (250 pmol/L biotin) vs. 40 +/- 2.0 (10,000 pmol/L biotin). Cells responded to biotin deficiency with increased expression of biotin transporter genes. Biotin-deficient cells maintained normal biotinylation of histones but contained reduced levels of biotinylated carboxylases, suggesting compartmentalization of intracellular biotin distribution. Rates of cell proliferation and activities of the apoptotic enzyme caspase-3 were similar among treatment groups, suggesting that net proliferation was not affected by biotin status. Net secretion of interleukin-2 by Jurkat cells was inversely associated with the biotin concentration in media [kU/(L x 24 h x 10(6) cells)]: 21 +/- 1.8 (25 pmol/L biotin) vs. 15 +/- 5.4 (250 pmol/L biotin) vs. 6.1 +/- 1.8 (10,000 pmol/L biotin), suggesting increased secretion or decreased internalization of interleukin-2 by biotin-deficient cells. This study provides evidence that biotin supply affects biotinylation of proteins, gene expression and metabolism of interleukin-2 in Jurkat cells. The physiological significance of effects of biotin status on metabolism of interleukin-2 remains to be elaborated.
Manthey
Karoline C
KC
Department of Nutritional Science and Dietetics, University of Nebraska at Lincoln, Lincoln, NE 68583-0806, USA.
Griffin
Jacob B
JB
Zempleni
Janos
J
D001710:Biotin / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D019921:Biotinylation; D002262:Carboxy-Lyases / Q000378:metabolism*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells / Q000187:drug effects / Q000201:enzymology*; D043586:Methylmalonyl-CoA Decarboxylase; D014158:Transcription, Genetic
D003470:Culture Media; D006657:Histones; D007376:Interleukin-2; D001710:Biotin; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase