Referenced in: none

Automatically associated channels: SK1

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

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

Journal, date & volume: J. Biol. Chem., 2008 Mar 21 , 283, 7657-65

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18211888

Abstract
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/gp91(phox), 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 P2X(7) 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 P2X(7) receptor is required for ATP-induced apoptosis in macrophages.