title: The protective effect of L-cysteine and glutathione on the adult and aged rat brain (Na+,K+)-ATPase and Mg2+-ATPase activities in galactosemia in vitro.
abstract: The aim of this study was to evaluate whether the addition of the antioxidants L-cysteine (Cys) or the reduced glutathione (GSH) could reverse the alterations of brain total antioxidant status (TAS) and the modulated activities of the enzymes (Na+,K+)-ATPase, and Mg2+-ATPase in adult or aged rat brain homogenates induced by galactosemia in vitro. Mixture A [mix. A: galactose-1-phosphate (Gal-1-P, 2 mM) plus galactitol (Galtol, 2 mM) plus galactose (Gal, 4 mM) = classical galactosemia] or mixture B [mix. B: Galtol (2 mM) plus Gal (1 mM) = galactokinase deficiency galactosemia] were preincubated in the presence or absence of Cys (0.83 mM) or GSH (0.83 mM) with adult or aged brain homogenates at 37 degrees C for 1 h. TAS and the enzyme activities were determined spectrophotometrically. Mix. A or mix. B preincubation with the adult brain resulted in a significant (Na+,K+)-ATPase inhibition (-30%) and a Mg2+-ATPase stimulation (+300% and +33%, respectively), whereas lower modifications of the enzyme activities (p < 0.001) were found in the aged brain. Gal mixtures decreased TAS by 40% (p < 0.001) and by 20% (p < 0.01) in adult and aged samples, respectively. The antioxidants significantly increased TAS resulting in the reversion of (Na+,K+)-ATPase inhibition and Mg2+-ATPase stimulation by mix. B only. The inhibitory effect of Gal and its derivatives on brain (Na+,K+)-ATPase and their stimulatory effect on Mg2+-ATPase are being decreased with age, probably due to the producion of free radicals. Cys and GSH increased TAS resulting in a reversion of the inhibited (Na+,K+)-ATPase in both models of the in vitro galactosemia and the stimulated Mg2+-ATPase in galactokinase deficiency galactosemia only.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Athens, Greece. stsakir@cc.uoa.gr
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
authors.forename: Haris
authors.initials: H
authors.lastname: Carageorgiou
authors.forename: Kleopatra H
authors.initials: KH
authors.lastname: Schulpis
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects* / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D005693:Galactosemias / Q000378:metabolism*; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013347:Subcellular Fractions / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D003545:Cysteine