論文 - 詳細
| RRC ID | 38136 |
|---|---|
| 著者 | Takenouchi T, Tsukimoto M, Iwamaru Y, Sugama S, Sekiyama K, Sato M, Kojima S, Hashimoto M, Kitani H. |
| タイトル | Extracellular ATP induces unconventional release of glyceraldehyde-3-phosphate dehydrogenase from microglial cells. |
| ジャーナル | Immunol Lett |
| Abstract |
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that is predominantly localized in the cytoplasm. However, recent studies have suggested that GAPDH is released by various cells and that extracellular GAPDH is involved in the regulation of neuritogenesis in neuronal cells. It has also been reported that GAPDH is expressed on the surfaces of macrophages and functions as a transferrin receptor. However, since GAPDH is a leaderless protein the mechanisms by which it reaches the extracellular environment remain unclear. Here, we examined the role of P2X7 receptor (P2X7R), an ATP-gated cation channel, in the unconventional release of GAPDH from microglial cells, the resident macrophages in the brain. The activation of P2X7R by ATP triggered GAPDH release from lipopolysaccharide (LPS)-primed microglial cells. ATP-induced microvesicle formation, exosome release, and K(+) efflux followed by caspase-1 activation are likely involved in the GAPDH release, but ATP-induced dilatation of membrane pores and lysosome exocytosis are not. It was also demonstrated that exogenous GAPDH facilitated LPS-induced phosphorylation of p38 MAP kinase in microglial cells. These findings suggest that P2X7R plays an important role in the unconventional release of GAPDH from microglial cells, and the GAPDH released into the extracellular space might be involved in the regulation of the neuroinflammatory response in the brain. |
| 巻・号 | 167(2) |
| ページ | 116-24 |
| 公開日 | 2015-10-1 |
| DOI | 10.1016/j.imlet.2015.08.002 |
| PII | S0165-2478(15)30016-X |
| PMID | 26277554 |
| MeSH | Adenosine Triphosphate / metabolism* Caspase 1 / metabolism Cells, Cultured Enzyme Activation Enzyme-Linked Immunosorbent Assay Exocytosis / immunology Extracellular Space Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism* Humans Immunohistochemistry Lipopolysaccharides / immunology Lysosomes / immunology Lysosomes / metabolism Microglia / immunology* Microglia / metabolism* Phosphorylation Potassium / metabolism Primary Cell Culture Receptors, Purinergic P2X7 / metabolism p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 3.276 |
| 引用数 | 17 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |