Antioxidant Function of the Mitochondrial Protein SP-22 in the Cardiovascular System

Abstract

The mitochondrial protein SP-22 has recently been reported to be a member of the thioredoxin-dependent peroxide reductase family, suggesting that it may be one of the antioxidant systems in mitochondria, which are the major site of reactive oxygen intermediate generation. The aim of this study was to examine whether SP-22 is involved in mitochondrial antioxidant mechanisms and whether its expression is induced by oxidative stresses, particularly those in mitochondria. The expression of SP-22 protein was enhanced by about 1.5-4.6-fold when bovine aortic endothelial cells (BAEC) were exposed to various oxidative stresses, including mitochondrial respiratory inhibitors which increased the superoxide generation in BAEC mitochondria. The expression of SP-22 mRNA increased 2.0-3.5-fold with a peak at 3-6 h after exposure to Fe2+/dithiothreitol or a respiratory inhibitor, antimycin A. BAEC with an increased level of SP-22 protein caused by pretreatment with mild oxidative stress became tolerant to subsequent intense oxidative stress. On the other hand, BAEC that had been depleted of SP-22 with an antisense oligodeoxynucleotide against SP-22 mRNA became more labile to oxidative stress than control BAEC. The induction of SP-22 protein by oxidative stress in vivo was demonstrated in an experimental model of myocardial infarction in rat heart. These findings indicate that SP-22 functions as an antioxidant in mitochondria of the cardiovascular system.

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].…”

Peroxiredoxin, a Novel Family of Peroxidases

“…SP-22 (Prx III) was also induced when bovine aortic endothelial cells were exposed to various oxidative stresses, including mitochondrial respiratory inhibitors, which increase superoxide and H 2 O 2 generation in mitochondria (1). The bovine aortic endothelial cells with an elevated level of Prx III as the result of exposure to mild oxidative stress became more tolerant to subsequent intense oxidative stress (1).…”

Mitochondrial Thioredoxin System

“…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). Prdx3 was identified as a target gene of nuclear c-Myc and shown to be essential for maintaining mitochondrial mass and transmembrane potential in transformed rat and human cells (33).…”