Coordinate effects of P2X7 and extracellular acidification in microglial cells

Ponarulselvam Sekar, Duen Yi Huang, Shwu Fen Chang, Wan Wan Lin

研究成果: 雜誌貢獻文章

3 引文 (Scopus)

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.

原文英語
頁(從 - 到)12718-12731
頁數14
期刊Oncotarget
9
發行號16
DOIs
出版狀態已發佈 - 一月 1 2018

指紋

Adenosine Triphosphate
Reactive Oxygen Species
Nigericin
Mitochondrial Dynamics
Inflammation
Acidosis
Immunity
Neoplasms
Potassium
Respiration
Cell Death
Calcium
Growth

ASJC Scopus subject areas

  • Oncology

引用此文

Coordinate effects of P2X7 and extracellular acidification in microglial cells. / Sekar, Ponarulselvam; Huang, Duen Yi; Chang, Shwu Fen; Lin, Wan Wan.

於: Oncotarget, 卷 9, 編號 16, 01.01.2018, p. 12718-12731.

研究成果: 雜誌貢獻文章

Sekar, Ponarulselvam ; Huang, Duen Yi ; Chang, Shwu Fen ; Lin, Wan Wan. / Coordinate effects of P2X7 and extracellular acidification in microglial cells. 於: Oncotarget. 2018 ; 卷 9, 編號 16. 頁 12718-12731.
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