Identification of a superoxide-generating NADPH oxidase system in human fibroblasts.
Human fibroblasts have the capacity to release superoxide radicals upon stimulation of an electron transport system similar to the NADPH oxidase of leukocytes. Two components of the NADPH oxidase system, (1) a flavoprotein of 45 kDa which binds diphenylene iodonium (a compound described as a specific inhibitor of the leukocyte NADPH oxidase), and (2) a low-potential cytochrome b, are present in fibroblast membranes. Fibroblasts exhibit these compounds at lower concentrations than do polymorphonuclear leukocytes or B-lymphocytes. The superoxide-generating system is rather uniformly associated with the outer cell membrane, as shown by light and electron microscopy. Superoxide release upon stimulation with various agents was prevented by the addition of micromolar concentrations of diphenylene iodonium, making an NADPH oxidase a likely source.
Meier
B
B
Chemisches Institut, Tierärztliche Hochschule, Hannover, Federal Republic of Germany.
Cross
A R
AR
Hancock
J T
JT
Kaup
F J
FJ
Jones
O T
OT
D000001:Calcimycin / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003573:Cytochrome b Group / Q000378:metabolism; D004579:Electron Transport; D005347:Fibroblasts / Q000201:enzymology* / Q000648:ultrastructure; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019255:NADPH Oxidases; D009861:Onium Compounds / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D003573:Cytochrome b Group; D005609:Free Radicals; D009861:Onium Compounds; D013481:Superoxides; D000001:Calcimycin; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases