Hypoxia effects on muscles: Everest climbers in proteomics study
- Published: Jan 8, 2015
- Author: Steve Down
- Channels: Proteomics & Genomics / Proteomics
I suspect that many of you, like myself, are planning to take a little more exercise in the coming weeks to fight off the ravages of the seasonal celebrations. While such plans are laudable, it is sensible to follow the usual advice to take it easy to begin with and build up slowly, whether you are walking, running, cycling, or in the gym. It is easy to do too much too soon and injure yourself in the eagerness to get fit.
For experienced climbers who take to the mountains, a different problem can present itself due to the thinner air that they meet as they ascend to greater heights. Oxygen deprivation affects the metabolism in the body so that it can cope with the reduced amount available and maintain normal tissue functions. The same effects can occur for patients with respiratory problems or heart disease.
Some work has been carried out to study the effects of hypoxia on muscle tissue using biochemical and morphological analyses on people at ground level and at altitude. Other studies have indicated that some enzymes are affected by reductions in the amount of available oxygen.
Now, this knowledge has been extended by a team of European researchers who used proteomics techniques to study the effects of hypoxia on the muscles of a team of climbers from the 2007 Caudwell expedition to Mount Everest. Skeletal muscles were chosen as they are influenced by oxygen consumption in a major way. Cecilia Gelfi from the University of Milan and scientists based in the UK at Southampton, Cambridge and London, described their approach in Proteomics.
The target muscle was the vastus lateralis which is on the side of the thigh. Biopsies were taken from 11 people in London who had not climbed or undergone hypoxic training for at least three months. After travelling to Nepal, they trekked to base camp at 5300 m. Five lab staff stayed here and biopsies were taken six days after their arrival, which was 19 days from the beginning of the trek. The remaining six climbed to 8848 m before returning to base camp where further biopsies were taken, equivalent to 66 days from the start of the trek.
The proteins in the muscles from the two altitude groups were separated and compared by 2D difference gel electrophoresis and the results were validated by immunoblotting. Any proteins of interest were identified by mass spectrometry and grouped according to their functions.
A total of 33 spots had altered abundances between the 19-day and 66-day altitude groups and they were attributed to aerobic and anaerobic metabolic processes, stress response, and structural or contractile proteins.
Enzymes altered by hypoxia
Among several altered pathways, there was a 30% reduction in the abundance of enzymes controlling the glycogen catabolism after 19 days but this appeared to be partly normalised after 66 days. Other pathways remained unbalanced, including the ATP cycle and glucose metabolism.
Aerobic pathways that were affected included the tricarboxylic acid (TCA) cycle, fatty acid metabolism and oxidative phosphorylation, all of which were also afflicted by a reduction in enzyme concentrations.
When the enzymatic processes were examined more closely, it was revealed that important adaptive mechanisms involved some key steps. In particular, the reduction of α-ketoglutarate in the TCA cycle resulted in increased levels of coenzyme A and is implicated in the rise in the hypoxia inducible factor prolyl hydroxlyase 2. The activity of glutamine synthetase, calcium ion release and antioxidant defences were also affected by reduced oxygen levels.
The affected processes were described in detail by the researchers and go some way to explaining how the human body copes with long-term hypoxia. The conclusions are also relevant for clinical research, indicating how the body reacts when it is starved of oxygen in some critical illnesses and events such as cardiac disease and respiratory problems.
Proteomics 2015, 15, 160-171: "Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest"
Article by Steve Down
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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