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

José Magalhães , Rita Ferreira , Maria J Neuparth , Paulo J Oliveira , Franklim Marques , António Ascensão , José Magalhães (1)

1 Research Center in Physical Activity, Health and Leisure

The effect of vitamin E on mice skeletal muscle mitochondrial dysfunction and oxidative damage induced by an in vivo acute and severe hypobaric hypoxic insult (48h at a barometric pressure equivalent to 8500m) was analyzed. Twenty-four male mice were randomly divided into the following 4 groups (n=6): control (C), hypoxia (H), vitamin E (VE; 60mg.kg -1} i.p., 3 times/wk for 3 wks) and hypoxia+VE (HVE). Significant increase in mitochondrial protein carbonyls groups (CGs) was found in H compared to C. Mitochondrial respiration was significantly impaired in H as demonstrated by decreased state 3, respiratory control ratio (RCR), lag phase and ADP/O, as well as by the enhanced state 4 using both complex I and II-linked substrates. Hypoxia also decreased the respiratory rates with CCCP and increased oligomycin-inhibited respiration using malate-piruvate (MP) as substrates. Hypoxia exposure per se increased Bax content and decreased Bcl-2/Bax ratio, while 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 the levels of CGs, state 3 with MP, RCR, ADP/O, lag phase and state CCCP, and abolished hypoxia-induced changes in state oligomycin and state 4. Vitamin E supplementation also re-established the Bax and Bcl-2/Bax ratio impairments caused by hypoxia, as well as the decreased inner and outer mitochondrial membrane integrity. In conclusion, data suggest that vitamin E prevents mitochondrial dysfunction and the activation of the intrinsic signaling pathway of apoptotic cell death induced by severe hypobaric hypoxia in mice skeletal muscle.

Mots clés: Medicine

José Magalhães, Rita Ferreira, Maria J Neuparth, Paulo J Oliveira, Franklim Marques, et al.. Vitamin E prevents hypobaric hypoxia-induced mitochondrial dysfunction in skeletal muscle. Clinical Science, 2007, 113 (12), pp.459-466. ⟨10.1042/CS20070075⟩. ⟨hal-00479371⟩