The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress.
The selenoprotein thioredoxin reductase (TrxR1) is an essential antioxidant enzyme known to reduce many compounds in addition to thioredoxin, its principle protein substrate. Here we found that TrxR1 reduced ubiquinone-10 and thereby regenerated the antioxidant ubiquinol-10 (Q10), which is important for protection against lipid and protein peroxidation. The reduction was time- and dose-dependent, with an apparent K(m) of 22 microm and a maximal rate of about 12 nmol of reduced Q10 per milligram of TrxR1 per minute. TrxR1 reduced ubiquinone maximally at a physiological pH of 7.5 at similar rates using either NADPH or NADH as cofactors. The reduction of Q10 by mammalian TrxR1 was selenium dependent as revealed by comparison with Escherichia coli TrxR or selenium-deprived mutant and truncated mammalian TrxR forms. In addition, the rate of reduction of ubiquinone was significantly higher in homogenates from human embryo kidney 293 cells stably overexpressing thioredoxin reductase and was induced along with increasing cytosolic TrxR activity after the addition of selenite to the culture medium. These data demonstrate that the selenoenzyme thioredoxin reductase is an important selenium-dependent ubiquinone reductase and can explain how selenium and ubiquinone, by a combined action, may protect the cell from oxidative damage.
Xia
Ling
L
Department of Microbiology, Pathology, and Immunology, Division of Pathology, F46, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden.
Nordman
Tomas
T
Olsson
Jerker M
JM
Damdimopoulos
Anastassios
A
Björkhem-Bergman
Linda
L
Nalvarte
Ivan
I
Eriksson
Lennart C
LC
Arnér
Elias S J
ES
Spyrou
Giannis
G
Björnstedt
Mikael
M
D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003067:Coenzymes; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009154:Mutation; D018384:Oxidative Stress; D051381:Rats; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors; D014162:Transfection; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000931:Antidotes; D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; C026663:ubiquinol-10; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D013880:Thioredoxin-Disulfide Reductase; C516126:Txnrd1 protein, rat; C024989:coenzyme Q10; C025204:Ubiquinone Q2