Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2) incorporates DHA into phospholipids and has possible functions for fatty acid-induced cell death
Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2) incorporates DHA into phospholipids and has possible functions for fatty acid-induced cell death
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DOI：
10.1016/j.bbrc.2020.03.074
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发表时间：
2020-05-21
影响因子：
3.1
通讯作者：
Shimizu, Takao
中科院分区：
文献类型：
--
作者：
Eto, Miki;Shindou, Hideo;Shimizu, Takao
甘油磷脂是生物膜的主要成分之一，由甘油-3-磷酸通过从头合成途径合成，并通过重塑途径重组。溶血磷脂酰基乙醇胺酰基转移酶2(LPEAT2)是重塑途径中发挥作用的酶之一，已有报道具有LPEAT、溶血磷脂酰胆碱酰基转移酶(LPCAT)和溶血磷脂酰甘油酰基转移酶(LPGAT)活性，供体为16：0-CoA、18：0-CoA和18：1-CoA。在本研究中，我们发现LPEAT2与22：6-CoA结合具有活性。利用Neuro 2A细胞进行的基因敲除研究表明，LPEAT2具有22：6-CoA的内源性LPEAT活性，并且LPEAT2具有调节22：6/20：4磷脂比例的功能。此外，我们还证明，在22：6(DHA)的补充下，过表达LPEAT2的Neuro 2A细胞在分化为神经元样细胞时会出现细胞死亡和坏死形态。这些结果表明，LPEAT2在诱导DHA依赖的细胞死亡中起作用。这项研究将有助于更好地了解DHA水平是如何在磷脂中调节的，特别是在LPEAT2高表达的大脑中。我们的研究也为理解DHA诱导细胞死亡的机制提供了洞察力。(C)2020作者。由爱思唯尔公司出版。
Glycerophospholipids, one of the main constituents of biological membranes, are synthesized from glycerol-3-phosphate through the de novo pathway, and are reconstituted through the remodeling pathway. Lysophosphatidylethanolamine acyltransferase 2 (LPEAT2), one of the enzymes that play a role in the remodeling pathway, has been previously reported to have LPEAT, lysophosphatidylcholine acyltransferase (LPCAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities with 16:0-CoA, 18:0-CoA, and 18:1-CoA as donors. In this study, we found that LPEAT2 is active with 22:6-CoA. Knockdown studies using Neuro 2A cells showed that LPEAT2 has endogenous LPEAT activity with 22:6-CoA, and that LPEAT2 has functions for modulating 22:6/20:4 ratios of phospholipids. In addition, we demonstrated that Neuro 2A cells overexpressing LPEAT2 underwent cell death with necrotic morphology when differentiated into neuron-like cells, with supplementation with 22:6 (DHA). These results suggest that LPEAT2 plays a role in inducing cell death DHA-dependently. This study will lead to better understand how DHA levels are regulated in phospholipids, especially in the brain where LPEAT2 is highly expressed. Our study also provides insight to understand the mechanism of cell death induced by DHA. (C) 2020 The Authors. Published by Elsevier Inc.