Antioxidant supplementation enhances the exercise-induced increase in mitochondrial uncoupling protein 3 and endothelial nitric oxide synthase mRNA content in human skeletal muscle.
The effects of acute exercise on the mRNA content of selected genes were examined during control conditions and after oral intake of antioxidants. In addition, to provide evidence for formation of reactive oxygen species (ROS) in human skeletal muscle during exercise, cytochrome c reduction was measured in microdialysate from the muscle. For the study on the effects of antioxidants on mRNA content, seven healthy, habitually active, male subjects participated in a double-blinded experimental design in which they, on one occasion, received a placebo and, on another, a mixture of antioxidants containing 1500 mg vitamin C, 120 mg coenzyme Q, and 345 mg alpha-tocopherol every day for 7 days before the experiment. On the experimental day the subjects cycled for 90 min and muscle biopsies were taken preexercise and at 1, 3, and 5 h after exercise. Exercise induced an increase in the eNOS, UCP3, PGC-1alpha, VEGF, Hsp72, and HO-1 mRNA content (p < 0.001), whereas there was no change in the Hsc70 mRNA level. Prior antioxidant treatment further enhanced (p < 0.05) the eNOS and UCP3 mRNA content after exercise. Moreover, the overall level of Hsc70 mRNA tended (p = 0.07) to be higher after antioxidant treatment. In another group of healthy male subjects, cytochrome c reduction was determined in microdialysate from the thigh muscle at rest and during knee extensor exercise to determine ROS formation. There was a significant increase in cytochrome c reduction with exercise both at 14 ( approximately 25%) and at 30 W ( approximately 50%). The data show that ROS are formed within skeletal muscle during exercise and that oral intake of antioxidants can enhance the exercise-induced adaptive mRNA responses of eNOS and UCP3.
Hellsten
Ylva
Y
Department of Exercise and Sport Science, Copenhagen Muscle Research Center, University of Copenhagen, DK-2100 Copenhagen, Denmark. yhellsten@aki.ku.dk
Nielsen
Jens J
JJ
Lykkesfeldt
Jens
J
Bruhn
Maria
M
Silveira
Leonardo
L
Pilegaard
Henriette
H
Bangsbo
Jens
J
D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D003067:Coenzymes / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D000071247:Uncoupling Protein 3; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; D003067:Coenzymes; D050883:HSC70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D014157:Transcription Factors; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014451:Ubiquinone; D045304:Cytochromes c; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C024989:coenzyme Q10; D024502:alpha-Tocopherol; D001205:Ascorbic Acid