title: Hypoxic responses of Na+/K+ ATPase in trout hepatocytes.
abstract: Reduction in oxygenation induces inhibition of Na+/K+ ATPase in a number of cells and tissues, including hepatocytes. When not reversed, decrease in Na+/K+ pump activity leads to a gradual Na+ accumulation, cell swelling and death. However, when accompanied by suppression of dissipative cation pathways, it has also been shown to be a beneficial adaptive strategy used by some hypoxia-tolerant species to reduce ATP consumption during prolonged periods of anoxia. This study aims to investigate acute hypoxic responses of the Na+/K+ ATPase in primary cultures of trout hepatocytes. Gradual decrease in oxygenation was followed by an instantaneous transient dose-dependent downregulation of the Na+/K+ ATPase transport activity, but was without an effect on hydrolytic function of the enzyme. Hypoxia-induced inhibition of active K+ influx was reversed spontaneously when hypoxic incubation time exceeded 20 min. The stimulating effect of prolonged hypoxic exposure on the Na+/K+ pump is most probably secondary to hypoxia-induced activation of the Na+/H+ exchanger with the following Na+ accumulation leading to Na+/K+ ATPase activation. Hypoxia-induced inhibition of the Na+/K+ pump was not caused by ATP depletion or global oxidative stress. However, local controlled production of reactive oxygen species seems to play an important role in hypoxia-induced regulation of the Na+/K+ ATPase. Treatment of cells with mercaptopropionyl glycine (MPG), a scavenger of OH*-, abolished hypoxia-induced inhibition of the Na+/K+ ATPase. Earlier on we have shown that activation of Na+/H+ exchanger under hypoxic conditions can be opposed by MPG treatment as well. Taken together our results suggest that regulation of both oxygen-sensitive transporters may be accomplished by local changes in free radical production.
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland. annab@access.unizh.ch
authors.forename: A
authors.initials: A
authors.lastname: Bogdanova
authors.forename: B
authors.initials: B
authors.lastname: Grenacher
authors.forename: M
authors.initials: M
authors.lastname: Nikinmaa
authors.forename: M
authors.initials: M
authors.lastname: Gassmann
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism*; D008163:Luminescent Measurements; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000494:pharmacology
chemical_list: C110658:N-(2-mercaptoproprionyl)-glycine; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D010100:Oxygen; D005998:Glycine