https://scholars.lib.ntu.edu.tw/handle/123456789/550429
標題: | Coordinate effects of P2X7 and extracellular acidification in microglial cells | 作者: | Sekar P. Huang D.-Y. Chang S.-F. WAN-WAN LIN |
關鍵字: | Acidification; ATP; Mitochondrial fission; Mitochondrial respiration; P2X7 | 公開日期: | 2018 | 卷: | 9 | 期: | 16 | 起(迄)頁: | 12718-12731 | 來源出版物: | Oncotarget | 摘要: | Extracellular adenosine 5'-triphosphate (ATP) is a damage-associated molecular pattern and contributes to inflammation associated diseases including cancer. Extracellular acidosis is a novel danger signal in the inflammatory sites, where it can modulate inflammation, immunity and tumor growth. Extracellular acidification was shown to inhibit P2X7-mediated channel currents, while it remains unknown how acidification and P2X7 together affect cellular responses. Here, we treated BV-2 microglial cells with ATP in a short period (< 15 min) or a sustained acidified condition. For short acidification we compared the actions of neutralized ATP and acidic ATP in a condition with pH buffering. For sustained acidification, we treated cells with neutralized ATP in acidic medium or acidic ATP in medium without pH buffering. In the short acidified condition, neutralized ATP induced higher responses than acidic ATP to increase intracellular calcium and reactive oxygen species, decrease intracellular potassium and induce cell death. In contrast, these cellular responses and mitochondrial fission caused by neutralized ATP were enhanced by pH 6.0 and pH 4.5 media. P2X7 activation can also rapidly block mitochondrial ATP turnover and respiration capacity, both of which were mimicked by nigericin and enhanced by acidity. Taken together P2X7-mediated ionic fluxes and reactive oxygen species production are attenuated under short acidification, while sustained acidification itself can induce mitochondrial toxicity which deteriorates the mitochondrial function under P2X7 activation. ? Sekar et al. |
URI: | 2-s2.0-85042559144 https://scholars.lib.ntu.edu.tw/handle/123456789/550429 |
ISSN: | 19492553 | DOI: | 10.18632/oncotarget.24331 | SDG/關鍵字: | adenosine triphosphate; nigericin; purinergic P2X7 receptor; reactive oxygen metabolite; acidification; acidity; Article; BV 2 cell; calcium cell level; cell death; cell pH; cell structure; controlled study; cytotoxicity; microglia; mitochondrial dynamics; mitochondrial membrane potential; mitochondrial respiration; potassium cell level |
顯示於: | 藥理學科所 |
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