| First Author | Jeong H | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 485 |
| Issue | 2 | Pages | 301-306 |
| PubMed ID | 28223219 | Mgi Jnum | J:251106 |
| Mgi Id | MGI:6102528 | Doi | 10.1016/j.bbrc.2017.02.087 |
| Citation | Jeong H, et al. (2017) TRPM2 contributes to LPC-induced intracellular Ca(2+) influx and microglial activation. Biochem Biophys Res Commun 485(2):301-306 |
| abstractText | Microglia are the resident immune cells which become activated in some pathological conditions in central nervous system (CNS). Lysophosphatidylcholine (LPC), an endogenous inflammatory phospholipid, is implicated in immunomodulatory function of glial cells in the CNS. Although several studies uncovered that LPC induces intracellular Ca(2+) influx and morphologic change in microglia, there is still no direct evidence showing change of phosphorylation of mitogen-activated protein kinase (MAPK) p38 (p-p38), a widely used microglia activation marker, by LPC. Furthermore, the cellular mechanism of LPC-induced microglia activation remains unknown. In this study, we found that LPC induced intracellular Ca(2+) increase in primary cultured microglia, which was blocked in the presence of Gd(3+), non-selective transient receptor potential (TRP) channel blocker. RT-PCR and whole cell patch clamp recordings revealed molecular and functional expression of TRP melastatin 2 (TRPM2) in microglia. Using western blotting, we also observed that LPC increased phosphorylation of p38 MAPK, and the increase of p-p38 expression is also reversed in TRPM2-knockout (KO) microglia. Moreover, LPC induced membrane trafficking of TRPM2 and intrathecal injection of LPC increased Iba-1 immunoreactivity in the spinal cord, which were significantly reduced in KO mice. In addition, LPC-induced intracellular Ca(2+) increase and inward currents were abolished in TRPM2-KO microglia. Taken together, our results suggest that LPC induces intracellular Ca(2+) influx and increases phosphorylation of p38 MAPK via TRPM2, which in turn activates microglia. |
