Hormone- and growth factor-stimulated NADH oxidase.
An NADH oxidase activity of animal and plant plasma membrane is described that is stimulated by hormones and growth factors. In plasma membranes of cancer cells and tissues, the activity appears to be constitutively activated and no longer hormone responsive. With drugs that inhibit the activity, cells are unable to grow although growth inhibition may be more related to a failure of the cells to enlarge than to a direct inhibition of mitosis. The hormone-stimulated activity in plasma membranes of plants and the constitutively activated NADH oxidase in tumor cell plasma membranes is inhibited by thiol reagents whereas the basal activity is not. These findings point to a thiol involvement in the action of the activated form of the oxidase. NADH oxidase oxidation by Golgi apparatus of rat liver is inhibited by brefeldin A plus GDP. Brefeldin A is a macrolide antibiotic inhibitor of membrane trafficking. A model is presented where the NADH oxidase functions as a thiol-disulfide oxidoreductase activity involved in the formation and breakage of disulfide bonds. The thiol-disulfide interchange is postulated as being associated with physical membrane displacement as encountered in cell enlargement or in vesicle budding. The model, although speculative, does provide a basis for further experimentation to probe a potential function for this enzyme system which, under certain conditions, exhibits a hormone- and growth factor-stimulated oxidation of NADH.
Department of Medicinal Chemistry and Pharmacognosy, Purdue University, West Lafayette, Indiana 47907.
D J
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Morré
D000818:Animals; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology; D003553:Cystine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006056:Golgi Apparatus / Q000201:enzymology; D006133:Growth Substances / Q000494:pharmacology*; D006367:HeLa Cells / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010940:Plant Proteins / Q000378:metabolism; D011490:Protein Disulfide Reductase (Glutathione) / Q000378:metabolism; D051381:Rats
D003517:Cyclopentanes; D006133:Growth Substances; D006728:Hormones; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010940:Plant Proteins; D020126:Brefeldin A; D003553:Cystine; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D011490:Protein Disulfide Reductase (Glutathione)