Misiti, Francesco

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Francesco Misiti

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Journal of Sport and Health Science

Exercise vs. high altitude therapy

IRIS Unicas (Università degli Studi di Cassino e del Lazio Meridionale)

Letter to the editorExercise vs. high altitude therapyFrancesco Misiti*Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino 03043, ItalyReceived 16 June 2017; revised 19 June 2017; accepted 20 June 2017Available onlineDear Editor,The metabolic and therapeutic effects of regular exercise onlifestyle-related chronic disease have been long established, butthe molecular bases for adaptive changes in metabolic functionsremain 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), localizedon the external face of erythrocytes, induced by a signalingpathway involving adenosine binding to the specific erythrocyteadenosine receptor A2B (ADORA2B). This eENT1 deletionallows for rapid accumulation of plasma adenosine to counter-act hypoxic tissue damage. Of note, reduced eENT1 resultingfrom initial hypoxia is maintained upon re-ascent in humans orre-exposure to hypoxia in mice.The reported plasma adenosine levels were almost doubleupon re-ascent to high altitude than on the first hypoxia expo-sure at the same altitude for 1 day.1 Intriguingly, sphingosine1-phosphate (S-1P), a bioactive signaling lipid generated athigh levels in erythrocytes, responsible for triggering O2 deliv-ery under hypoxic conditions, displayed the same trend aselevated extracellular adenosine.2 Interestingly, the role ofadenosine in adaptive mechanisms has also been implicated inthe field of exercise training.3 Exercise affects the purinergicsystem in erythrocytes and platelets.4 In particular, increases inadenosine triphosphate (ATP) and its metabolites in bloodplasma following exercise have been related to the ability of redblood cells to release ATP in areas of low oxygen tension, aswell to rise ectonucleotidase (NTPDase) activities in plateletsand red blood cells. It would be interesting to evaluate the levelsof 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 mechanisminvolved in exercise training. It should be noted that theseresults could be of interest for our understanding of the mecha-nisms underlying hypoxia related pathologic conditions, suchas cardiovascular, hemolytic, and respiratory diseases, and themaintenance of metabolic and functional capacity with aging.More experimental data are needed to confirm the mechanismsreported here. Nonetheless, eENT1 and S1P in erythrocytesmay enhance the effects of exercise training without exposureto high altitude. Exercise intervention is an effective and inex-pensive alternative to high altitude therapy, easy to access, andnot limited to geographic conditions and timing of exposure tohigh altitudes.Competing interestsThe author declares that he has no competing interests.References1. Song A, Zhang Y, Han L, Yegutkin GG, Liu H, Sun K, et al. Erythrocytesretain hypoxic adenosine response for faster acclimatization upon re-ascent.Nat Commun 2017;8:14108. doi:10.1038/ncomms141082. Sun K, Zhang Y, D’Alessandro A, Nemkov T, Song A, Wu H, et al.Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygenrelease for adaptation to high-altitude hypoxia. Nat Commun 2016;7:12086.doi:10.1038/ncomms120863. Simpson RE, Phillis JW. Adenosine in exercise adaptation. Br J Sports Med1992;26:54–8.4. Gorman MW, Rooke GA, Savage MV, Jayasekara MP, Jacobson KA, FeiglEO. Adenine nucleotide control of coronary blood flow during exercise. AmJ Physiol Heart Circ Physiol 2010;299:H1981–9.*E-mail address: f.misiti@unicas.ithttp://dx.doi.org/10.1016/j.jshs.2017.07.0022095-2546/© 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-NDlicense (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.2017.07.002Available online at www.sciencedirect.comJournal of Sport and Health Science xx (2017) 1–1www.jshs.org.cnQ2Q11bs_bs_query2bs_bs_query3bs_bs_query4bs_bs_query5bs_bs_query6bs_bs_query7bs_bs_query8bs_bs_query9bs_bs_query10bs_bs_query11bs_bs_query12bs_bs_query13bs_bs_query14bs_bs_query15bs_bs_query16bs_bs_query17bs_bs_query18bs_bs_query19bs_bs_query20bs_bs_query21bs_bs_query22bs_bs_query23bs_bs_query24bs_bs_query25bs_bs_query26bs_bs_query27bs_bs_query28bs_bs_query29bs_bs_query30bs_bs_query31bs_bs_query32bs_bs_query33bs_bs_query34bs_bs_query35bs_bs_query36bs_bs_query37bs_bs_query38bs_bs_query39bs_bs_query40bs_bs_query41bs_bs_query42bs_bs_query43bs_bs_query44bs_bs_query45bs_bs_query46bs_bs_query47bs_bs_query48bs_bs_query49bs_bs_query50bs_bs_query51bs_bs_query52bs_bs_query53bs_bs_query54bs_bs_query55bs_bs_query56bs_bs_query57bs_bs_query58bs_bs_query59bs_bs_query60bs_bs_query61bs_bs_query62bs_bs_query63bs_bs_query64bs_bs_query65bs_bs_query66bs_bs_query67bs_bs_query68bs_bs_query69bs_bs_query70bs_bs_query71bs_bs_query72bs_bs_query73bs_bs_query74bs_bs_query75bs_bs_query76bs_bs_query77bs_bs_query78bs_bs_queryH O S T E D  BYProduction and hosting by ElsevierAvailable online at www.sciencedirect.comScienceDirectScienceDirect

Exercise  vs.  high altitude therapy

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Exercise vs. high altitude therapy

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