Unitary model of cell activation, growth control, cancer and other diseases: 1. Activated oxygen species and arachidonic acid modulation of solute permeabilities, internal Ca, Na and AOS levels and DNA transcription and synthesis.
A comprehensive model of cellular activation and proliferation is developed. The model has arachidonic acid (ARA) produced mainly from PLA2 on both sides of the membrane, and superoxide and other activated oxygen species (AOS) formed from O2 by electrons passing out through membrane NANPH and NADH oxidases, as the immediate stimulants of solute permeability. Both ARA and AOS interact with the various solute channel proteins especially their external thiols and disulfides, to increase influx of metabolic substrates, Na, Ca and O2. PLA2 and NADPH oxidase are turned on by growth factors at their receptors acting through tyrosine kinase phosphorylations of messenger proteins GP and ras p-21, stimulated proteases, and by Ca-calmodulin. The adenylate cyclase system has opposite, deactivating character as it increases efflux of Ca and desensitizes growth factor receptors by phosphorylation to shut down the increased solute permeability. Most cancer types are due to carcinogen binding to cell membrane channel and mitochondrial sites for increased solute influx with excessive AOS production inside the cell from mitochondria and other vesicles. High Ca, Na and AOS stimulate proliferation with extra high levels causing transformation to the autogenic, more embryonic-type cancer cell.
B
B
Doonan
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology*; D010100:Oxygen / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014158:Transcription, Genetic
D016718:Arachidonic Acid; D004247:DNA; D012964:Sodium; D010100:Oxygen; D002118:Calcium