Adenine nucleotide translocase 2, a putative target protein for 2-carba cyclic phosphatidic acid in microglial cells

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. •ANT2 as a 2ccPA-interacting protein in BV-2 cells.•2ccPA inhibited PAO-induced depolarization and apoptosis in BV-2 cells.•PAO mediated ROS generation was blocked by 2ccPA.•2ccPA decreased the PAO-induced intracellular ATP concentration.•PAO-induced phosphorylation of p38 MAPK was blocked by 2ccPA.