Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages
Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages
复制标题
溶血磷脂酰肌醇酰基转移酶 1 参与巨噬细胞胞质 Ca2+ 振荡
DOI：
10.1111/gtc.12681
复制
发表时间：
2019
期刊：
影响因子：
2.1
通讯作者：
Hazeki Kaoru
中科院分区：
文献类型：
--
作者：
Takemasu Shinya;Ito Masaki;Morioka Shin;Nigorikawa Kiyomi;Kofuji Satoshi;Takasuga Shunsuke;Eguchi Satoshi;Nakanishi Hiroki;Matsuoka Isao;Sasaki Junko;Sasaki Takehiko;Hazeki Kaoru
溶血磷脂酰肌醇-酰基转移酶-1(LPIAT1)特异性催化花生四烯酰辅酶A向溶血磷脂酰肌醇转移。LPIAT−/−小鼠已经被证明在大脑和肝脏有严重的缺陷；然而，这些情况背后的确切分子机制还不是很清楚。由于免疫细胞参与了基于LPIAT1功能障碍的肝脏炎症，我们使用shRNA和CRISPR/Cas9产生了LPIAT1缺陷的Raw264.7巨噬细胞。这些细胞中C38：4物种的数量明显减少，尤其是PtdInsP2。与野生型细胞不同，LPIAT1基因缺陷的细胞在UDP刺激下表现出细胞内钙离子的长时间振荡，这被认为是通过GQ偶联的P2Y6受体激活磷脂酶Cβ，即使在没有细胞外钙的情况下也是如此。推测钙离子反应延长可能与LPIAT1功能障碍引起的肝脏炎症风险增加有关。
Lysophosphatidylinositol‐acyltransferase‐1 (LPIAT1) specifically catalyzes the transfer of arachidonoyl‐CoA to lysophosphoinositides. LPIAT−/−mice have been shown to have severe defects in the brain and liver; however, the exact molecular mechanisms behind these conditions are not well understood. As immune cells have been implicated in liver inflammation based on disfunction of LPIAT1, we generated Raw264.7 macrophages deficient in LPIAT1, using shRNA and CRISPR/Cas9. The amount of C38:4 species in phosphoinositides, especially in PtdInsP2, was remarkably decreased in these cells. Unlike in wild‐type cells, LPIAT1‐deficient cells showed prolonged oscillations of intracellular Ca2+upon UDP stimulation, which is known to activate phospholipase Cβ through the Gq‐coupled P2Y6 receptor, even in the absence of extracellular Ca2+. It is speculated that the prolonged Ca2+response may be relevant to the increased risk of liver inflammation induced by LPIAT1 disfunction.