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Clinical Science (2007) 113, (459–466) (Printed in Great Britain)

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Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle

José MAGALHÃES*†, Rita FERREIRA*, Maria J. NEUPARTH*, Paulo J. OLIVEIRA‡§, Franklim MARQUES¶ and António ASCENSÃO*†

*Research Center in Physical Activity, Health and Leisure, University of Porto, 4200-450 Porto, Portugal, †Department of Sport Biology, University of Porto, 4200-450 Porto, Portugal, ‡Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal, §Centre of Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbria, Portugal, Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Porto, 4099-030 Porto, Portugal, and ¶Institute for Molecular and Cell Biology, University of Porto, 4099-030 Porto, Portugal

Key words: apoptotic signalling, antioxidant, high altitude, membrane integrity, mitochondrial dysfunction, vitamin E (a-tocopherol).

Abbreviations: ADP/O, ratio between the amount of ADP phosphorylated per oxygen consumed; AIF, apoptosis-inducing factor; BHT, butylated hydroxytoluene; CCCP, carbonyl cyanide m-chlorophenylhydrazone; CG, carbonyl group; DNPH, dinitrophenylhydrazine; M+P, malate (2 mmol/l) plus pyruvate (5 mmol/l); PTP, permeability transition pore; RCR, respiratory control ratio; RONS, reactive oxygen and nitrogen species; S+R, succinate (10 mmol/l) plus rotenone (4 mmol/l); TBS, Tris-buffered saline.

Correspondence: Dr José Magalhães, at the Research Centre in Physical Activity, Health and Leisure, University of Porto, 4200-450 Porto, Portugal (email jmaga@fcdef.up.pt).

In the present study, the effect of vitamin E (a-tocopherol) on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48 h at a barometric pressure equivalent to 8500 m) has been investigated. Male mice (n=24) were randomly divided into the following four groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60 mg/kg of body weight intraperitoneally, three times/week for 3 weeks) and hypoxia+VE (HVE). A significant increase in mitochondrial protein CGs (carbonyl groups) was found in the H group compared with the C group. Confirming previous observations from our group, hypoxia induced mitochondrial dysfunction, as identified by altered respiratory parameters. Hypoxia exposure increased Bax content and decreased the Bcl-2/Bax ratio, whereas Bcl-2 remained unchanged. Inner and outer mitochondrial membrane integrity were significantly affected by hypoxia exposure; however, vitamin E treatment attenuated the effect of hypoxia on mitochondrial oxidative phosphorylation and on the levels of CGs. Vitamin E supplementation also prevented the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decrease in inner and outer mitochondrial membrane integrity. In conclusion, the results suggest that vitamin E prevents the loss of mitochondrial integrity and function, as well as the increase in Bax content, which suggests that mitochondria are involved in increased cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

Received 2 March 2007/9 May 2007; accepted 18 June 2007

Published as Immediate Publication 18 June 2007, doi:10.1042/CS20070075

© The Authors Journal compilation © 2007 Biochemical Society