Relationship between intracellular pH changes, activation of protein kinase C and NADPH oxidase in macrophages.
Activation of the superoxide-generating NADPH oxidase by phorbol ester or zymosan induced a cytoplasmic acidification when liver macrophages were incubated in sodium-free media or in the presence of amiloride. Staurosporine or desensitization of protein kinase C inhibited phorbol ester- and zymosan-induced pH changes and generation of superoxide. The intracellular pH remained unchanged in cells incubated in physiological sodium media. Ionomycin and arachidonic acid did not induce a change in intracellular pH or a generation of superoxide. Fluoride, which has been shown to induce a translocation of protein kinase C in these cells, did not elicit superoxide generation but induced a decrease in intracellular pH. These experiments support (1) a role of the Na+/H+ antiporter in macrophages as a metabolic regulator of intracellular pH upon stimulation of the superoxide-generating NADPH oxidase, and (2) suggest an involvement of protein kinase C in this process.
Dieter
P
P
Biochemisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007399:Interphase / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D015054:Zymosan / Q000494:pharmacology
D002352:Carrier Proteins; D010703:Phorbol Esters; D017923:Sodium-Hydrogen Exchangers; D016718:Arachidonic Acid; D015759:Ionomycin; D015054:Zymosan; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D005459:Fluorides