title: Parvalbumin as a metal-dependent antioxidant.
abstract: Parvalbumin (PA) is a Ca(2+)-binding protein of vertebrates massively expressed in tissues with high oxygen uptake and respectively elevated level of reactive oxygen species (ROS). To characterize antioxidant properties of PA, antioxidant capacity (AOC) of intact rat α-PA has been explored. ORAC, TEAC and hydrogen peroxide AOC assays evidence conformation-dependent oxidation of the PA. AOC value for the apo-PA 4-11-fold exceeds that for the Ca(2+)-loaded protein. Despite folded conformation of apo-PA, it has AOC equivalent to that of the proteolized protein. The most populated under resting conditions PA form, Mg(2+)-bound PA, has AOC similar to that of apo-PA. ROS-induced changes in absorption spectrum of PA evidence an oxidation of PA's phenylalanines in the ORAC assay. Sensitivity of PA oxidation to its conformation enabled characterization of its metal affinity and pH-dependent behavior: a transition with pKa of 7.6 has been revealed for the Ca(2+)-loaded PA. Since total AOC of PA under in vivo conditions may reach the level of reduced glutathione, we propose that PA might modulate intracellular redox equilibria and/or signaling in a calcium-dependent manner. We speculate that the oxidation-mediated damage of some of PA-GABAergic interneurons observed in schizophrenia is due to a decline in total AOC of the reduced glutathione-PA pair.
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region, 142290, Russia; Department of Biomedical Engineering, Pushchino State Institute of Natural Sciences, Pushchino, Moscow region, 142290, Russia.
authors.forename: Sergei E
authors.initials: SE
authors.lastname: Permyakov
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region, 142290, Russia.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Kazakov
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region, 142290, Russia. Electronic address: avkhacheva@gmail.com.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Avkhacheva
authors.affiliation: Protein Research Group, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region, 142290, Russia; Department of Biomedical Engineering, Pushchino State Institute of Natural Sciences, Pushchino, Moscow region, 142290, Russia.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Permyakov
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000737:chemistry*; D010084:Oxidation-Reduction; D010320:Parvalbumins / Q000737:chemistry*; D051381:Rats; D017382:Reactive Oxygen Species / Q000737:chemistry; D013696:Temperature
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D008670:Metals; D010320:Parvalbumins; D017382:Reactive Oxygen Species
keywords: Antioxidant activity; Calcium-binding proteins; Free radicals; Oxidative stress; Parvalbumin; Redox reactions; Redox signaling; Schizophrenia