期刊
CELLULAR SIGNALLING
卷 82, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2021.109951
关键词
Pull-down assay; Lipid-protein interaction; 2ccPA; Microglia; ROS; Intracellular ATP; Apoptosis
类别
资金
- Japan Society for the Promotion of Science [19K07322, 19K07098]
- Japan Science and Technology Agency [PROJECT-07050777]
- MEXT Project for the promotion of public utilization of advanced research infrastructure (Program for supporting the introduction of the new sharing system) [JPMXS0422500320]
- Ochanomizu University
- Strasbourg University
- Grants-in-Aid for Scientific Research [19K07322, 19K07098] Funding Source: KAKEN
This study identified the interaction between a metabolically stabilized cPA derivative, 2ccPA, and ANT2 in microglial cells, showing its ability to inhibit apoptosis induced by phenylarsine oxide and improve cell survival.
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.
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