Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, Canada; and.
J Lipid Res. 2013 Oct;54(10):2665-77. doi: 10.1194/jlr.M037044. Epub 2013 Jul 26.
Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood. In this study FA-GPL remodeling was investigated in resting and proliferating primary human T cells. Significant changes were measured in the composition and distribution of FAs in GPLs following receptor activation of human T cells. The FA distribution of proliferating T cells was very similar to that of the human Jurkat T cell line and when the stimulus was removed from proliferating T cells, they stopped proliferating and the FA distribution largely reverted back to that of resting T cells. The cellular content of saturated and monounsaturated FAs was significantly increased in proliferating cells, which was associated with an induction of FA synthase and stearoyl-CoA desaturase-1 gene expression. Additionally, cellular arachidonate was redistributed in GPLs in a distinct pattern that was unlike any other FAs. This redistribution was associated with an induction of CoA-dependent and CoA-independent remodeling. Accordingly, significant changes in the expression of several acyl-CoA synthetases, lysophospholipid acyltransferases, and phospholipase A2 were measured. Overall, these results suggest that metabolic pathways are activated in proliferating T cells that may represent fundamental changes associated with human cell proliferation.
脂肪酸(FA)和甘油磷脂(GPL)代谢随细胞周期进入而发生的变化尚未完全阐明。在这项研究中,研究了静止和增殖的原代人 T 细胞中 FA-GPL 的重塑。人 T 细胞受体激活后,GPL 中 FA 的组成和分布发生了显著变化。增殖 T 细胞的 FA 分布与人类 Jurkat T 细胞系非常相似,当刺激从增殖 T 细胞中去除时,它们停止增殖,FA 分布在很大程度上恢复为静止 T 细胞的分布。增殖细胞中饱和和单不饱和 FA 的细胞含量显著增加,这与 FA 合酶和硬脂酰辅酶 A 去饱和酶-1 基因表达的诱导有关。此外,细胞花生四烯酸在 GPL 中的重分布呈现出与其他 FA 不同的独特模式。这种重分布与 CoA 依赖性和 CoA 非依赖性重塑的诱导有关。相应地,测量了几种酰基辅酶 A 合成酶、溶血磷脂酰基转移酶和磷脂酶 A2 的表达的显著变化。总体而言,这些结果表明,增殖 T 细胞中激活了代谢途径,这可能代表与人类细胞增殖相关的基本变化。