title: Regulation of the frontocortical sodium pump by Na+ in Alzheimer's disease: difference from the age-matched control but similarity to the rat model.
abstract: The Na+ and K+ dependence of the frontocortical Na,K-ATPase in Alzheimer's disease (AD) was compared with that in human control (Co) and rat AD model. In AD, the relationship between the Na/K ratio and the Na,K-ATPase activity showed noticeable left-shift with three-fold increase in the enzyme affinity for Na+ (K(0.5)=10 and 30 mM in AD and Co, respectively). The Na+ dependence of the enzyme in AD showed two different Hill coefficients (n(H)), 1.1 and 0.3, whereas the Co value of n(H) was higher (1.4). The rat AD model generated by ibotenic acid revealed a Na+ dependence similar to AD. The K+ dependence of the Na,K-ATPase showed no significant difference in AD and Co. Compared with Co, AD produced a shift in the break of the Na,K-ATPase Arrhenius plot, suggesting remarkable alterations in the enzyme lipid environment. Our findings support the hypothesis that dysfunction of the Na,K-ATPase in AD is provoked by altered Na+ dependence of the enzyme. An impairment of the pump functionality might serve as an early mechanism of AD that should be interrupted by selective pharmacological agents.
authors.affiliation: Department of Biochemistry, Tartu University, Ravila 19, Tartu, Estonia.
authors.forename: Czeslava
authors.initials: C
authors.lastname: Kairane
authors.forename: Kristiina
authors.initials: K
authors.lastname: Roots
authors.forename: Tanel
authors.initials: T
authors.lastname: Uusma
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Ello
authors.initials: E
authors.lastname: Karelson
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.forename: Mihkel
authors.initials: M
authors.lastname: Zilmer
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D005625:Frontal Lobe / Q000201:enzymology*; D006801:Humans; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013045:Species Specificity; D013696:Temperature
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium