Decrease in membrane phospholipid unsaturation induces unfolded protein response.
Decrease in membrane phospholipid unsaturation induces unfolded protein response.
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DOI：
10.1074/jbc.m110.126870
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发表时间：
2010-07-16
期刊：
影响因子：
--
通讯作者：
Arai H
中科院分区：
文献类型：
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作者：
Ariyama H;Kono N;Matsuda S;Inoue T;Arai H
在哺乳动物细胞和组织中，各种脂肪酸分布于膜磷脂中。膜磷脂中脂肪酸不饱和度影响许多膜相关功能，并且可受到饮食和脂质代谢酶（如脂肪酸去饱和酶）活性改变的影响。然而，很少有人知道哺乳动物细胞如何应对磷脂脂肪酸组成的变化。在这项研究中，我们表明，硬脂酰辅酶A去饱和酶1（SCD 1）敲低增加了磷脂中饱和脂肪酸的量，减少了单不饱和脂肪酸的量，而不影响游离脂肪酸的量或组成，并诱导未折叠蛋白反应（UPR），通过C/EBP同源蛋白（CHOP）和葡萄糖调节蛋白78（GRP 78）mRNA的表达增加以及Xbox结合蛋白1（XBP 1）mRNA的剪接证实。SCD 1敲除诱导的UPR可被各种不饱和脂肪酸挽救，并被饱和脂肪酸增强。溶血磷脂酰胆碱酰基转移酶3（LPCAT 3），它优先将多不饱和脂肪酸磷脂酰胆碱，上调SCD 1敲除细胞。LPCAT 3的敲低协同增强了UPR与SCD 1敲低。最后，我们发现，棕榈酸诱导的UPR显着增强LPCAT 3敲除以及SCD 1敲除。这些结果表明，膜磷脂不饱和度的降低诱导UPR。
Various kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues. The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by diet and by altered activities of lipid-metabolizing enzymes such as fatty acid desaturases. However, little is known about how mammalian cells respond to changes in phospholipid fatty acid composition. In this study we showed that stearoyl-CoA desaturase 1 (SCD1) knockdown increased the amount of saturated fatty acids and decreased that of monounsaturated fatty acids in phospholipids without affecting the amount or the composition of free fatty acid and induced unfolded protein response (UPR), evidenced by increased expression of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) mRNAs and splicing of Xbox-binding protein 1 (XBP1) mRNA. SCD1 knockdown-induced UPR was rescued by various unsaturated fatty acids and was enhanced by saturated fatty acid. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), which incorporates preferentially polyunsaturated fatty acids into phosphatidylcholine, was up-regulated in SCD1 knockdown cells. Knockdown of LPCAT3 synergistically enhanced UPR with SCD1 knockdown. Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR.