Antioxidant function of the mitochondrial protein SP-22 in the cardiovascular system

The mitochondrial protein SP-22 has recently been reported to be a member o f the thioredoxin-dependent peroxide reductase family, suggesting that it m ay be one of the antioxidant systems in mitochondria, which are the major s ite of reactive oxygen intermediate generation, The aim of this study was t o 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 abou t 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 express ion of SP-22 mRNA increased 2.0-3.5-fold with a peak at 3-6 h after exposur e to Fe2+/dithiothreitol or a respiratory inhibitor, antimycin A. BAEC with an increased level of SP-22 protein caused by pretreatment with mild oxida tive stress became tolerant to subsequent intense oxidative stress. On the other hand, BAEC that had been depleted of SP-22 with an antisense oligodeo xynucleotide against SP-22 mRNA became more labile to oxidative stress than control BAEC. The induction of SP-22 protein by oxidative stress in vivo w as demonstrated in an experimental model of myocardial infarction in rat he art. These findings indicate that SP-22 functions as an antioxidant in mito chondria of the cardiovascular system.