title: Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans.
abstract: Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-alpha-tocopherol 400 IU/day + ascorbic acid (AA) 500 mg/day (CEalpha), RRR-alpha-tocopherol 290 IU/day + RRR-gamma-tocopherol 130 IU/day + AA 500 mg/day (CEalphagamma), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, alpha-tocopherol, gamma-tocopherol, AA, and 8-iso-prostaglandin-F2alpha (8-PGF2alpha). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF2alpha, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEalpha. In Control, skeletal muscle HSP72 mRNA content increased 2.5-fold (P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEalpha, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEalphagamma. The results indicate that gamma-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.
authors.affiliation: Centre of Inflammation and Metabolism, The Department of Infectious Diseases and The Copenhagen Muscle Research Centre, Rigshospitalet and The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. cfischer@dadlnet.dk
authors.forename: Christian P
authors.initials: CP
authors.lastname: Fischer
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Hiscock
authors.forename: Samar
authors.initials: S
authors.lastname: Basu
authors.forename: Bengt
authors.initials: B
authors.lastname: Vessby
authors.forename: Anders
authors.initials: A
authors.lastname: Kallner
authors.forename: Lars-Börje
authors.initials: LB
authors.lastname: Sjöberg
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry; D009638:Norepinephrine / Q000097:blood; D020033:Protein Isoforms / Q000032:analysis / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014810:Vitamin E / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000097:blood / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000097:blood / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D050884:HSP72 Heat-Shock Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D024504:gamma-Tocopherol; D015237:Dinoprost; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine