Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent

Anren Song, Yujin Zhang, Leng Han, Gennady G. Yegutkin, Hong Liu, Kaiqi Sun, Angelo D’Alessandro, Jessica Li, Harry Karmouty-Quintana, Takayuki Iriyama, Tingting Weng, Shushan Zhao, Wei Wang, Hongyu Wu, Travis Nemkov, Andrew W. Subudhi, Sonja Jameson- Van Houten, Colleen G. Julian, Andrew T. Lovering, Kirk C. Hansen, Hong Zhang, Mikhail Bogdanov, William Dowhan, Jianping Jin, Rodney E. Kellems, Holger K. Eltzschig, Michael Blackburn, Robert C. Roach and Yang Xia ()
Additional contact information
Anren Song: The University of Texas Health Science Center at Houston
Yujin Zhang: The University of Texas Health Science Center at Houston
Leng Han: The University of Texas Health Science Center at Houston
Gennady G. Yegutkin: Medicity Research Laboratory, University of Turku
Hong Liu: The University of Texas Health Science Center at Houston
Kaiqi Sun: The University of Texas Health Science Center at Houston
Angelo D’Alessandro: University of Colorado
Jessica Li: The University of Texas Health Science Center at Houston
Harry Karmouty-Quintana: The University of Texas Health Science Center at Houston
Takayuki Iriyama: The University of Texas Health Science Center at Houston
Tingting Weng: The University of Texas Health Science Center at Houston
Shushan Zhao: The University of Texas Health Science Center at Houston
Wei Wang: The University of Texas Health Science Center at Houston
Hongyu Wu: The University of Texas Health Science Center at Houston
Travis Nemkov: Altitude Research Center
Andrew W. Subudhi: Altitude Research Center
Sonja Jameson- Van Houten: Altitude Research Center
Colleen G. Julian: Altitude Research Center
Andrew T. Lovering: Altitude Research Center
Kirk C. Hansen: University of Colorado
Hong Zhang: MD Anderson Cancer Center
Mikhail Bogdanov: The University of Texas Health Science Center at Houston
William Dowhan: The University of Texas Health Science Center at Houston
Jianping Jin: The University of Texas Health Science Center at Houston
Rodney E. Kellems: The University of Texas Health Science Center at Houston
Holger K. Eltzschig: Organ Protection Program, University of Colorado School of Medicine
Michael Blackburn: The University of Texas Health Science Center at Houston
Robert C. Roach: Altitude Research Center
Yang Xia: The University of Texas Health Science Center at Houston

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) levels are reduced in humans at high altitude and in mice under hypoxia. eENT1 deletion allows rapid accumulation of plasma adenosine to counteract hypoxic tissue damage in mice. Adenosine signalling via erythrocyte ADORA2B induces PKA phosphorylation, ubiquitination and proteasomal degradation of eENT1. Reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice and accounts for erythrocyte hypoxic memory and faster acclimatization. Our findings suggest that targeting identified purinergic-signalling network would enhance the hypoxia adenosine response to counteract hypoxia-induced maladaptation.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14108

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DOI: 10.1038/ncomms14108

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