Adenine nucleotide translocase 2, a putative target protein for 2-carba cyclic phosphatidic acid in microglial cells
Adenine nucleotide translocase 2, a putative target protein for 2-carba cyclic phosphatidic acid in microglial cells
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腺嘌呤核苷酸转位酶 2，小胶质细胞中 2-碳环磷脂酸的假定靶蛋白
DOI：
10.1016/j.cellsig.2021.109951
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发表时间：
2021
影响因子：
4.8
通讯作者：
Murakami-Murofushi Kimiko
中科院分区：
文献类型：
--
作者：
Tsukahara Tamotsu;Sahara Yasuka;Ribeiro Nigel;Tsukahara Ryoko;Gotoh Mari;Sakamoto Satoshi;Handa Hiroshi;Murakami-Murofushi Kimiko
脂质-蛋白质相互作用在许多生物现象中起着重要作用。溶血磷脂介质，如环磷脂酸（cPA），已被公认为第二信使，但很少有cPA的细胞靶点已确定的日期。此外，激活这些下游信号事件的分子机制仍然未知。在这项研究中，使用代谢稳定的cPA卡巴衍生物（2ccPA）固定的磁珠，我们确定腺嘌呤核苷酸转位酶2（ANT 2）作为小胶质细胞中的2ccPA相互作用蛋白。测试2ccPA抑制小胶质细胞中由氧化苯胂引起的细胞凋亡的能力。这种损伤在2 ccPA处理后显著改善，沿着细胞增殖、凋亡、活性氧产生和细胞内ATP水平。这是第一份报告表明2ccPA与小胶质细胞中的ANT 2直接结合，并为2ccPA在保护小胶质细胞免受由ANT 2介导的信号通路诱导的凋亡性死亡方面的新益处提供了证据。
Lipid-protein interactions play essential roles in many biological phenomena. Lysophospholipid mediators, such as cyclic phosphatidic acid (cPA), have been recognized as secondary messengers, yet few cellular targets for cPA have been identified to date. Furthermore, the molecular mechanism that activates these downstream signaling events remains unknown. In this study, using metabolically stabilized cPA carba-derivative (2ccPA)-immobilized magnetic beads, we identified adenine nucleotide translocase 2 (ANT2) as a 2ccPA-interacting protein in microglial cells. 2ccPA was tested for its ability to inhibit apoptosis caused by phenylarsine oxide in microglial cells. This damage was significantly improved upon 2ccPA treatment, along with cell proliferation, apoptosis, reactive oxygen species production, and intracellular ATP levels. This is the first report to suggest the direct binding of 2ccPA to ANT2 in microglial cells and provides evidence for a new benefit of 2ccPA in protecting microglial cells from apoptotic death induced by the ANT2-mediated signaling pathway.