2007, Piran, Slovenia

Altitude Physiology
vastus lateralis protein maps were obtained from 15 mg bioptic samples taken from
the mid portion of the vastus lateralis muscle and analyzed by mass spectrometry in:
A) three groups of Asian subjects: 1) first generation high altitude tibetan natives
recently migrated to Kathmandu, Tib1; 2) second generation lowland Tibetans never
exposed to high altitude before, Tib2; 3) Nepali lowlanders of Aryan ethnicity, N and
in:
B) a group of élite caucasian mountaineers before and after 10 to 12 weeks exposure
to altitudes comprised between 5000 to 8850 meters during expeditions to Mt. Lhotse
and Mt. Everest in Nepal.
RESULTS
A) The following proteins were found to be differentially expressed in the muscle of
the three investigated Asian groups (Gelfi et al., 2004):
-Glutathione-S-Transferase P1-1 (GST P1-1) which was overexpressed in both Tib1
(+380%) and Tib2 (+50%) compared to N. This is an enzyme that conjugating
molecules of reduced glutathione to a series of electrophilic acceptors, plays a potent
detoxifying role in cells exposed to ROS.
-Delta 2-enoyl-CoA hydratase (ECH), an intra-mitochondrial enzyme involved in
beta-oxidation of fatty acids, which is upregulated in both Tib1 and Tib2.
-Glyceraldehyde-3-phosphate(GAPDH) and lactate dehydrogenase (LDH), two
glycolytic enzymes, both downregulated in Tib1.
-Myoglobin (Mb), whose isoform at pH=7.29, appears to be upregulated in both
Tibetan groups.
-Phosphoglycerate mutase (PGA), the enzyme converting glycerate-phosphate to
glycerate 2-phosphate which is 50% higher in Tib1 than in Tib2 and N.
-NADH-ubiquinone oxidoreductase (NUGM), an enzyme of the respiratory chain,
which is 30% overexpressed in Tib1 compared to Tib2.
On the whole, Tib1 and, to some extent, Tib2 appear to be better protected than N
against ROS. Tib1 are also characterized by metabolic adaptations compatible with a
tighter coupling of ATP demand and supply.
B) Neither protein changes of the type found for Tib1 and Tib2 nor protein carbonyl
derivatives accumulation were observed in caucasian mountaineers after prolonged
exposure to extreme altitude despite a substantial increase in lipofuscin accumulation
and a 25% reduction of the muscle mitochondrial volume density. Contractile
proteins were unaffected by hypoxia. However, post- vs. pre- hypoxia exposure
differential maps show significant upregulation of 10 molecules involved in anaerobic
and aerobic metabolism, in mitochondrial activity, as translation factors, in protein
synthesis and in the elimination of peroxidases together with a downregulation of a γactin
and of a hydrolase involved in the processing of ubiquitin precursors ( Cerretelli
et al., 2007). The found results do not feature any of the changes occurring in native
tibetan migrants, particularly the great increase of the ROS scavenger GST P1-1.
Contractile proteins, including myosin light chains, protein carbonyl derivatives (4-
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