Letter to the editor
Exercise vs. high altitude therapy
Francesco Misiti*
Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino 03043, Italy Received 16 June 2017; revised 19 June 2017; accepted 20 June 2017
Available online
Dear Editor,
The metabolic and therapeutic effects of regular exercise on lifestyle-related chronic disease have been long established, but the molecular bases for adaptive changes in metabolic functions remain an area of intense research.
Recently, an elegant study1
demonstrated that faster accli-matization to high altitude upon re-ascent depends on degrada-tion of equilibrative nucleoside transporter (eENT1), localized on the external face of erythrocytes, induced by a signaling pathway involving adenosine binding to the specific erythrocyte adenosine receptor A2B (ADORA2B). This eENT1 deletion allows for rapid accumulation of plasma adenosine to counter-act hypoxic tissue damage. Of note, reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice.
The reported plasma adenosine levels were almost double upon re-ascent to high altitude than on the first hypoxia expo-sure at the same altitude for 1 day.1 Intriguingly, sphingosine
1-phosphate (S-1P), a bioactive signaling lipid generated at high levels in erythrocytes, responsible for triggering O2
deliv-ery under hypoxic conditions, displayed the same trend as elevated extracellular adenosine.2 Interestingly, the role of
adenosine in adaptive mechanisms has also been implicated in the field of exercise training.3 Exercise affects the purinergic
system in erythrocytes and platelets.4In particular, increases in
adenosine triphosphate (ATP) and its metabolites in blood plasma following exercise have been related to the ability of red blood cells to release ATP in areas of low oxygen tension, as well to rise ectonucleotidase (NTPDase) activities in platelets and red blood cells. It would be interesting to evaluate the levels
of eENT1 and S1P in erythrocytes, after targeted exercise inter-ventions based on factors such as mode, intensity, or duration, with a translational perspective to an adaptive mechanism involved in exercise training. It should be noted that these results could be of interest for our understanding of the mecha-nisms underlying hypoxia related pathologic conditions, such as cardiovascular, hemolytic, and respiratory diseases, and the maintenance of metabolic and functional capacity with aging. More experimental data are needed to confirm the mechanisms reported here. Nonetheless, eENT1 and S1P in erythrocytes may enhance the effects of exercise training without exposure to high altitude. Exercise intervention is an effective and inex-pensive alternative to high altitude therapy, easy to access, and not limited to geographic conditions and timing of exposure to high altitudes.
Competing interests
The author declares that he has no competing interests.
References
1. Song A, Zhang Y, Han L, Yegutkin GG, Liu H, Sun K, et al. Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent. Nat Commun 2017;8:14108. doi:10.1038/ncomms14108
2. Sun K, Zhang Y, D’Alessandro A, Nemkov T, Song A, Wu H, et al. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia. Nat Commun 2016;7:12086. doi:10.1038/ncomms12086
3. Simpson RE, Phillis JW. Adenosine in exercise adaptation. Br J Sports Med 1992;26:54–8.
4. Gorman MW, Rooke GA, Savage MV, Jayasekara MP, Jacobson KA, Feigl EO. Adenine nucleotide control of coronary blood flow during exercise. Am J Physiol Heart Circ Physiol 2010;299:H1981–9.
*
E-mail address:f.misiti@unicas.it http://dx.doi.org/10.1016/j.jshs.2017.07.002
2095-2546/© 2017 Production and hosting by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ARTICLE IN PRESS
JSHS413_proof■ 13 July 2017 ■ 1/1Please cite this article in press as: Francesco Misiti, Exercise vs. high altitude therapy, Journal of Sport and Health Science (2017), doi:10.1016/j.jshs.2017.07.002
Available online atwww.sciencedirect.com
Journal of Sport and Health Science xx (2017) 1–1
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