Research press release


Nature Communications

Biological sciences: Blood cells "remember" how to acclimatize to altitude



今回、Yang Xiaの研究チームは、アデノシンシグナル伝達を増強する重要な構成要素が発見されたことを報告している。この研究で、高地に移動したヒトと低酸素環境下のマウスの両方において、赤血球タンパク質の1つであるeENT1が分解されていることが明らかになった。eENT1が失われると、アデノシンが血漿中に急速に蓄積し、低酸素症による組織損傷が抑制された。(ヒトの場合には)最初の登山時によるeENT1の減少が2度目の登山でも起こり、この赤血球による「低酸素症の記憶」が順応の加速につながった。


Humans generally acclimatize faster to high altitudes upon re-ascent, compared with the first ascent, because red blood cells "remember" the previous ascent and are able to adapt quickly, reports a study in Nature Communications this week. A key molecular pathway involved in this response is identified in both mice and humans, which may inform treatment avenues to mitigate the damaging effects of hypoxia (the reduced availability of oxygen to tissues).

To survive hypoxia our body undergoes adaptive responses to promote the delivery of oxygen to tissues. One such response is the release of a chemical called adenosine, which prevents vascular leakage, reduces inflammation and causes blood vessels to dilate to reduce tissue damage. Previous research has shown that repeated exposure to high altitudes results in a quicker adaption to the low-oxygen environment, but the molecular basis for this enhanced response has been unclear.

Yang Xia and colleagues report the discovery of a key component responsible for enhanced adenosine signalling. They find that a red-blood-cell protein called eENT1 is degraded both in humans moving to high altitudes and in mice in low-oxygen environments. Loss of this protein allows rapid accumulation of adenosine in the plasma to counteract hypoxic tissue damage. The depleted levels of eENT1 caused by the initial ascent (in humans) are maintained upon re-ascent, and this “hypoxic memory” of red blood cells leads to faster acclimatization.

The authors suggest that therapeutically targeting the eENT1 degradation pathway might guide efforts to combat the damaging effects of hypoxia, which can occur in a range of health conditions (such as cardiovascular or respiratory diseases) as well as when ascending to high altitudes.

doi: 10.1038/ncomms14108

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