Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 123, Issue 4, Pages 951-956Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00155.2017
Keywords
erythrocyte; hypoxia adaptation; adenosine signaling; sphingosine 1-phosphate; hypoxic memory
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Funding
- National Heart, Lung, and Blood Institute [HL-114457, HL-136969, HL-113574]
- U.S. Department of Defense [Telemedicine & Advanced Technology Research Center (TATRC)] [W81XWH-11-2-0040]
- Cardiopulmonary & Respiratory Physiology Laboratory, University of Oregon
- Charles S. Houston Endowed Professorship at the Altitude Research Center, School of Medicine, University of Colorado Anschutz Medical Campus
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Erythrocytes are vital to human adaptation under hypoxic conditions because of their abundance in number and irreplaceable function of delivering oxygen (O-2). However, although multiple large-scale altitude studies investigating the overall coordination of the human body for hypoxia adaptation have been conducted, detailed research with a focus on erythrocytes was missing due to lack of proper techniques. The recently maturing metabolomics profiling technology appears to be the answer to this limitation. Metabolomics profiling provides unbiased high-throughput screening data that reveal the overall metabolic status of erythrocytes. Recent studies have exploited this new technology and provided novel insight into erythrocyte physiology and pathology. In particular, a series of studies focusing on erythrocyte purinergic signaling have reported that adenosine signaling, coupled with 5' AMP-activated protein kinase (AMPK) and the production of erythrocyte-enriched bioactive signaling lipid sphingosine 1-phosphate, regulate erythrocyte glucose metabolism for more O-2 delivery. Moreover, an adenosine-dependent erythrocyte hypoxic memory was discovered that provides an explanation for fast acclimation upon re-ascent. These findings not only shed new light on our understanding of erythrocyte function and hypoxia adaptation, but also offer a myriad of novel therapeutic possibilities to counteract various hypoxic conditions.
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