title: [Oxidative modification of glyceraldehyde-3-phosphate dehydrogenase influences its interaction with endogenous neuroprotector isatin].
abstract: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classical glycolytic redox sensitive enzyme, exhibits various non-glycolytic functions, which are considered to be especially important for progression of various neurodegenerative diseases. GAPDH binds isatin (indole-dione-2,3), an endogenous indole often used as a parent component in numerous derivatives demonstrating diverse pharmacological (including neuroprotector) activities. In this study we have investigated binding of intact and mildly oxidized GAPDH to immobilized isatin, using an optical biosensor technique, employing surface plasmon resonance (SPR), and the effect of isatin as a probe for this binding. Mild GAPDH oxidation by 70 mM H(2)O(2) increased enzyme dissociation from immobilized isatin. Since GAPDH is considered as a putative target for various neuroprotector agents, this suggests that its redox state determines sensitivity to neuroprotective agents, and oxidative stress typical for various neurodegenerative disorders may significantly reduce pharmacological effectiveness of such compounds.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Buneeva
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: O V
authors.initials: OV
authors.lastname: Gnedenko
authors.affiliation: Moscow State University, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Medvedeva
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Ivanov
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A E
authors.initials: AE
authors.lastname: Medvedev
mesh_terms: D015374:Biosensing Techniques; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D007510:Isatin / Q000737:chemistry / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020349:Surface Plasmon Resonance
chemical_list: D018696:Neuroprotective Agents; D007510:Isatin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: glyceraldehyde-3-phosphate dehydrogenase; isatin; ligand-protein interaction; surface plasmon resonance optical biosensor