Related Experiment Video
Updated: Jun 17, 2026

In vivo Imaging Method to Distinguish Acute and Chronic Inflammation
Published on: August 16, 2013
Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca(2+)/c-Abl signaling pathway
Amina El Jamali1, Anthony J Valente, Robert A Clark
1Department of Medicine, University of Texas Health Science Center, and South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, TX 78229-3900, USA. AkoulouzeBik@uthscsa.edu
Abstract:
The importance of H(2)O(2) as a cellular signaling molecule has been demonstrated in a number of cell types and pathways. Here we explore a positive feedback mechanism of H(2)O(2)-mediated regulation of the phagocyte respiratory burst NADPH oxidase (NOX2). H(2)O(2) induced a dose-dependent stimulation of superoxide production in human neutrophils, as well as in K562 leukemia cells overexpressing NOX2 system components. Stimulation was abrogated by the addition of catalase, the extracellular Ca(2+) chelator BAPTA, the T-type Ca(2+) channel inhibitor mibefradil, the PKCdelta inhibitor rottlerin, or the c-Abl nonreceptor tyrosine kinase inhibitor imatinib mesylate or by overexpression of a dominant-negative form of c-Abl. H(2)O(2) induced phosphorylation of tyrosine 311 on PKCdelta and this activating phosphorylation was blocked by treatment with rottlerin, imatinib mesylate, or BAPTA. Rac GTPase activation in response to H(2)O(2) was abrogated by BAPTA, imatinib mesylate, or rottlerin. In conclusion, H(2)O(2) stimulates NOX2-mediated superoxide generation in neutrophils and K562/NOX2 cells via a signaling pathway involving Ca(2+) influx and c-Abl tyrosine kinase acting upstream of PKCdelta. This positive feedback regulatory pathway has important implications for amplifying the innate immune response and contributing to oxidative stress in inflammatory disorders.
Related Concept Videos
Peroxisomes
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Nitric Oxide Signaling Pathway
Electron Transport Chain: Complex III and IV
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of Angiogenesis and Blood Supply

