title: Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity.
abstract: The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe(2+)-mediated in vitro oxidative stress model. The results show that Fe(2+) inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe(2+) inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA) inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe(2+) may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe(2+) and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: T I
authors.initials: TI
authors.lastname: Omotayo
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: G S
authors.initials: GS
authors.lastname: Akinyemi
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: P A
authors.initials: PA
authors.lastname: Omololu
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: B O
authors.initials: BO
authors.lastname: Ajayi
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
authors.forename: A A
authors.initials: AA
authors.lastname: Akindahunsi
authors.affiliation: Centro de Ciencias Naturais e Exatas, Programa Posgraduacao em Bioquimica Toxciologica, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: J B T
authors.initials: JB
authors.lastname: Rocha
authors.affiliation: Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria. Electronic address: ijkade@yahoo.com.
authors.forename: I J
authors.initials: IJ
authors.lastname: Kade
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D002413:Cations, Divalent; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002413:Cations, Divalent; D013438:Sulfhydryl Compounds; D014810:Vitamin E; D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D007501:Iron; D000254:Sodium-Potassium-Exchanging ATPase; D004229:Dithiothreitol
keywords: Dithiothreitol; Electrogenic sodium pump; Iron; Oxidative stress; Thiol oxidation; Vitamin E