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 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.
Araki
M
M
Department of Health Development, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Nanri
H
H
Ejima
K
K
Murasato
Y
Y
Fujiwara
T
T
Nakashima
Y
Y
Ikeda
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002319:Cardiovascular System / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism; D018384:Oxidative Stress; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D012333:RNA, Messenger; D010544:Peroxidases; D054464:Peroxiredoxins