title: The arachidonate-activable, NADPH oxidase-associated H+ channel. Evidence that gp91-phox functions as an essential part of the channel.
abstract: The human neutrophil NADPH oxidase-associated H+ channel acts as a charge compensator for the electrogenic generation of superoxide (O2-.). The expression of the channel activity was found to increase in parallel with that of the stimulatable generation of O2-. in differentiated HL60 cells. HL60 cells induced to differentiate in the presence of succinyl acetone (a inhibitor of heme synthesis) were unable to generate O2-., failed to express p22-phox but retained H+ channel activity. EBV transformed B lymphocyte cell lines from normal and CGD patients lacking expression of either p47-phox or p67-phox all expressed unaltered channel activity; however, the activity was completely absent in the lymphocyte cell line lacking gp91-phox. CHO cells and undifferentiated HL60 cells transfected with gp91-phox cDNA expressed H+ channel activity correlating with the expression of gp91-phox. We therefore conclude that the large subunit of the NADPH oxidase cytochrome b (gp91-phox) is the arachidonate activable H+ channel of human neutrophils.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, United Kingdom.
authors.forename: L M
authors.initials: LM
authors.lastname: Henderson
authors.forename: G
authors.initials: G
authors.lastname: Banting
authors.forename: J B
authors.initials: JB
authors.lastname: Chappell
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001402:B-Lymphocytes; D001483:Base Sequence; D016466:CHO Cells; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D006224:Cricetinae; D018076:DNA, Complementary; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006921:Hygromycin B / Q000494:pharmacology; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids; D017494:Proton Pumps / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D017494:Proton Pumps; D011994:Recombinant Proteins; D013481:Superoxides; D016718:Arachidonic Acid; D006921:Hygromycin B; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase; D013755:Tetradecanoylphorbol Acetate