Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models expressing fatty acid desaturases

Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models expressing fatty acid desaturases
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DOI:
10.1093/abbs/gmt155
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发表时间:
2014-04-01
影响因子:
3.7
通讯作者:
Rimoldi, Omar J.
Rimoldi, Omar J.
中科院分区:
生物学3区
文献类型:
--
作者:
Jaureguiberry, Maria S.;Alejandra Tricerri, M.;Rimoldi, Omar J.

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实验证据表明,质膜 (PM) 相关信号传导以及细胞代谢和活力取决于脂质组成和组织。目前工作的目的是开发一种细胞模型来研究内源性多不饱和脂肪酸 (PUFA) 对 PM 特性的影响,并分析其对胆固醇 (Chol) 稳态的影响。我们之前已经证明,通过使用过度表达硬脂酰辅酶A去饱和酶的细胞系,膜组成和组织通过不同机制协调参与胆汁流出和细胞活力的细胞途径。现在,我们将研究扩展到过度表达三角 5 和三角 6 去饱和酶的细胞模型,这导致 PM 中的 PUFA 含量永久较高。此外,该细胞系表现出增加的 PM 流动性、胆汁储存和线粒体活性。此外,在这些细胞中,人载脂蛋白 A-I 介导的胆汁去除效率低于相应的对照细胞。综上所述,我们的结果表明,通过调节 PM 组织以及胆汁输出和体内平衡来保留细胞功能。
Experimental evidence has suggested that plasma membrane (PM)-associated signaling and hence cell metabolism and viability depend on lipid composition and organization. The aim of the present work is to develop a cell model to study the endogenous polyunsaturated fatty acids (PUFAs) effect on PM properties and analyze its influence on cholesterol (Chol) homeostasis. We have previously shown that by using a cell line over-expressing stearoyl-CoA-desaturase, membrane composition and organization coordinate cellular pathways involved in Chol efflux and cell viability by different mechanisms. Now, we expanded our studies to a cell model over-expressing both triangle 5 and triangle 6 desaturases, which resulted in a permanently higher PUFA content in PM. Furthermore, this cell line showed increased PM fluidity, Chol storage, and mitochondrial activity. In addition, human apolipoprotein A-I-mediated Chol removal was less efficient in these cells than in the corresponding control. Taken together, our results suggested that the cell functionality is preserved by regulating PM organization and Chol exportation and homeostasis.