SP‐22 is a Thioredoxin‐Dependent Peroxide Reductase in Mitochondria

Abstract

SP-22 is a mitochondrial antioxidant protein in bovine adrenal cortex. The protein is homologous to thioredoxin peroxidase and other antioxidant proteins. It protects radical-sensitive enzymes from oxidative damage by a radical-generating system (Fe'+/dithiothreitol ) in the presence of a small amount of serum. In this study we purified a second mitochondrial protein with M , 11 777, which cooperates with SP-22 to protect glutamine synthetase and other proteins from Fe2+/dithiothreitol-mediated damage. Without SP-22, the protein had no protecting activity. We determined amino acid and nucleotide sequences of the protein and its cDNA, respectively, and found that it was a protein of the thioredoxin family. The protein, designated as mt-Trx (mitochondrial thioredoxin), had a presequence composed of 59 amino acids that seemed to be a mitochondrial targeting signal.Mitochondria1 extract prepared from adrenal cortex contained NADPH-dependent 5,5'dithiobi@ni-trobenzoic acid) (Nbs,) reductase activity. The enzyme was thought to have thioredoxin reductase activity, since the Nbs,-reducing activity was stimulated by mt-Trx. We partially purified the Nbs, reductase from bovine adrenocortical mitochondria. In the presence of the partially purified reductase, mt-Trx, and NADPH, SP-22 showed the activity to protect oxyhemoglobin against ascorbate-induced damage. Furthermore, with the three protein components (Nbs, reductase, mt-Trx, and SP-22) NADPH was oxidized in the presence of hydrogen peroxide or tert-butyl hydroperoxide. The oxidation of NADPH was concomitant with the disappearance of an equimolar amount of hydrogen peroxide. Without any one of the protein components no hemoglobin-protecting and peroxide-dependent NADPH-oxidizing activities were observed. From these results we concluded that SP-22 is thioredoxin-dependent peroxide reductase or so-called thioredoxin peroxidase in mitochondria from the adrenal cortex.Keywords: thioredoxin peroxidase ; peroxide reductase; mitochondria; adrenal cortex.

Oxidative and nitrosative stress induces peroxiredoxins in pancreatic beta cells

“…Peroxiredoxins are in different subcellular compartments. While Prx III is localized to mitochondria [12,22,54,55], Prx I and Prx II are found in the cytoplasm [15,23,32,43]. Furthermore Prx I is thought to be translocated into the nucleus by association with other proteins such as tyrosine kinase c-Abl, though given its small size it could enter passively [34].…”

“…19] and catalyse reduction of both hydrogen peroxide and alkyl peroxides to water or to the corresponding alcohol using thioredoxin (Tx) as their physiological hydrogen donor [20,21,22,23,24]. Additionally it has been shown that the bacterial peroxiredoxin AhpC (alkylhydroperoxide reductase subunit C) is able to protect against nitrogen radicals [25].…”

Mitochondrial Thioredoxin System

“…Two mitochondrial Prdx isoforms have been identified so far. Prdx3, originally cloned from murine erythroleukemia cells (30), is exclusively detected in mitochondria (31). Prdx3 expression can be induced in response to oxidant treatments, and antisensemediated inhibition of Prdx3 expression was shown to sensitize bovine aortic endothelial cells to oxidative challenges (32).…”

Molecular characterization and expression analysis of six peroxiredoxin paralogous genes in gilthead sea bream (Sparus aurata): Insights from fish exposed to dietary, pathogen and confinement stressors

“…PRDX1 and 2, also referred as natural killer enhancing factors (NKEF-A, NKEF-B), are localized in the cytosol [6,7], whereas the other members of the 2-Cys PRDX subclass are widely distributed with PRDX3 in mitochondria [8], PRDX4 in endoplasmatic reticulum and extracellular space [9] and PRDX5 in cytosol, mitochondria and peroxisomes [10]. In contrast, PRDX6 is restricted to cytosol [11], and the catalytic efficiency of all PRDXs is less than that of catalase or glutathione peroxidases by one or three orders of magnitude [12].…”