Chemical hormesis in cell growth: a molecular target at the cell surface.
A multifunctional ubiquinol (NADH) oxidase with protein disulfide-thiol interchange activity of the cell surface, abbreviated as NOX, is described as a molecular target for chemical hormesis of cell growth. The activity of the NOX correlates with rate of cell enlargement, which helps to determine how rapidly cells will divide. When NOX activity is inhibited, cells fail to enlarge following division and the result is a population of small cells unable to reach the minimum size required for them to divide again. In plants, cells fail to enlarge when NOX activity is inhibited. When NOX activity is stimulated or constitutively activated, as in cancer, cells enlarge more rapidly and the rate of cell division also is enhanced. Both cell growth and NOX activity are sometimes stimulated by low concentrations of normally inhibitory molecules. These properties define chemical hormesis, making the NOX molecule a molecular target to explain hormetic growth responses and to utilize hormetic principles to increase, for example, crop yields with plants. The NOX activity at the cell surface oscillates with a temperature-compensated 24-min ultradian (<24 h) periodicity. The indicated function of the NOX protein as a time-keeping mechanism adds to its potential importance as a molecular target for chemical hormesis.
Morré
D J
DJ
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907-1333, USA.
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D018556:Crops, Agricultural; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D063245:Plant Development; D010944:Plants / Q000187:drug effects; D015262:Xenobiotics / Q000009:adverse effects
D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D015262:Xenobiotics; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases