Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAPK pathway for extracellular ATP-induced apoptosis in macrophage

Takuya Noguchi, Ken Ishii, Hisashi Fukutomi, Isao Naguro, Atsushi Matsuzawa, Kohsuke Takeda, Hidenori Ichijo

研究成果: Article査読

139 被引用数 (Scopus)

抄録

Extracellular ATP, an autocrine or paracrine intercellular transmitter, is known to induce apoptosis in macrophages. However, the precise signaling mechanisms of ATP-induced apoptosis remain to be elucidated. Here we showed that activation of p38 mitogen-activated protein kinase (MAPK) plays a critical role in ATP-induced apoptosis. p38 activation and apoptosis in macrophages were induced by ATP. ATP-induced apoptosis was mediated in part by production of reactive oxygen species (ROS) derived from NOX2/gp91phox, a component of the NADPH oxidase complex expressed in macrophages and neutrophils. Furthermore, ATP-induced ROS generation, p38 activation, and apoptosis were almost completely inhibited by selective P2X7 receptor antagonists. We also found that ATP-induced apoptosis were diminished in ASK1-deficient macrophages accompanied by the lack of p38 activation. These results demonstrate that ROS-mediated activation of the ASK1-p38 MAPK pathway downstream of P2X7 receptor is required for ATP-induced apoptosis in macrophages.

本文言語English
ページ(範囲)7657-7665
ページ数9
ジャーナルJournal of Biological Chemistry
283
12
DOI
出版ステータスPublished - 2008 3 21
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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