Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells
Biotin supply affects expression of biotin transporters, biotinylation of carboxylases and metabolism of interleukin-2 in Jurkat cells
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DOI：
10.1093/jn/132.5.887
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发表时间：
2002-05-01
影响因子：
4.2
通讯作者：
Zempleni, J
中科院分区：
文献类型：
--
作者：
Manthey, KC;Griffin, JB;Zempleni, J
生物素的供应可能会影响细胞中基因的转录和蛋白质的生物素化。在这项研究中，Jurkat 细胞用于模拟生物素供应对免疫细胞中生物素稳态和白细胞介素 2 代谢的影响。将细胞在含有缺乏（25 pmol/L）、生理浓度（250 pmol/L）或药理学浓度（10,000 pmol/L）生物素的培养基中培养4周。生物素依赖性酶丙酰辅酶A羧化酶的活性与培养基中的生物素浓度平行[pmol碳酸氢盐固定/(min x 10(6)细胞)]：1.9+/-0.7(25pmol/L生物素)与19+/-1.2(250pmol/L生物素)与40+/-2.0(10,000pmol/L生物素)。细胞通过增加生物素转运蛋白基因的表达来应对生物素缺乏。生物素缺陷细胞维持组蛋白的正常生物素化，但生物素化羧化酶水平降低，表明细胞内生物素分布的区室化。治疗组之间的细胞增殖率和凋亡酶 caspase-3 活性相似，表明净增殖不受生物素状态的影响。 Jurkat 细胞的 IL-2 净分泌量与培养基中的生物素浓度呈负相关 [kU/(L x 24 h x 10(6) cells)]：21 +/- 1.8 (25 pmol/L 生物素) vs. 15 +/- 5.4 (250 pmol/L 生物素) vs. 6.1 +/- 1.8 (10,000 pmol/L 生物素)，表明增加生物素缺陷细胞对白细胞介素 2 的分泌或内化减少。这项研究提供了证据，证明生物素供应会影响 Jurkat 细胞中蛋白质的生物素化、基因表达和白细胞介素 2 的代谢。生物素状态对 IL-2 代谢影响的生理意义仍有待详细阐述。
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.