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Review Article

Is Hypoxic/Altitude Training an Important Topic in the Field of Hypoxia?

Grégoire P. Millet1,2 ( )Martin Burtscher3Johannes Burtscher1,2
Institute of Sport Sciences, University of Lausanne, Campus Dorigny, 1015 Lausanne, Switzerland
Department of Biomedical Sciences, University of Lausanne, 1015 Lausanne, Switzerland
Department of Sport Science, University of Innsbruck, Innsbruck, Austria
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Abstract

Hypoxia is an essential topic in medical or biological sciences. The main aims of the present study were to examine the most important medical articles (i.e., the top 100 most cited) on hypoxia. We examine how the Nobel-prize awarded hypoxia inducible factor (HIF)-pathway discovery in the early 1990s has changed the thematic composition of this body of literature, with a special emphasis on the studies linking hypoxia and cancer. We searched Pubmed for articles with the terms #Hypox, #Altitude, or #Mountain in the title that have been published in biomedical journals and ranked the articles on their number of citations in Web of Science. A second search was performed in all journals for articles related to hypoxia and cancer. Strikingly, only 12 of the top-100 most-cited articles on hypoxia and only 3 articles of the top-100 articles related to cancer were published before 1995. Moreover, only 5 articles from prior 1995 reached 1000 citations, while 27 articles published in 1995 or later were cited more than 1000 times, most of them on the HIF-1 pathway. Eighty percent of the top-100 articles were related to the HIF pathway, while there were no articles on the application of hypoxia either for therapeutic use (i.e., hypoxic conditioning in patients) or for performance enhancement (i.e., altitude training in athletes). In conclusion, the early-1990s discovery of the HIF pathway and of its molecular regulation has shifted the focus of hypoxia research towards molecular mechanisms and consequences of tissue hypoxia, most notably in cancer. The importance of studies focusing on clinical and performance applications of systemic hypoxia is relatively lower.

References

1

An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha. Nature. 1998;392(6674):405–8.

2

Appelhoff RJ, Tian YM, Raval RR, Turley H, Harris AL, Pugh CW, Ratcliffe PJ, Gleadle JM. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem. 2004;279(37):38458–65.

3

Arany Z, Huang LE, Eckner R, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, Livingston DM. An essential role for p300/CBP in the cellular response to hypoxia. Proc Natl Acad Sci U S A. 1996;93(23):12969–73.

4

Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouysségur J, Mazure NM. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 2009;29(10):2570–81.

5

Berne RM. Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol. 1963;204:317–22.

6

Birner P, Schindl M, Obermair A, Plank C, Breitenecker G, Oberhuber G. Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 2000;60(17):4693–6.

7

Brezis M, Rosen S. Hypoxia of the renal medulla—its implications for disease. N Engl J Med. 1995;332(10):647–55.

8

Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997;38(2):285–9.

9

Brown JM. The hypoxic cell: a target for selective cancer therapy–eighteenth Bruce F. Cain Memorial Award lecture. Cancer Res. 1999;59(23):5863–70.

10

Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004;4(6):437–47.

11

Bruick RK. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A. 2000;97(16):9082–7.

12

Bunn HF, Poyton RO. Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev. 1996;76(3):839–85.

13
Burtscher J, Mallet RT, Burtscher M, Millet GP. Hypoxia and brain aging: neurodegeneration or neuroprotection? Ageing Res Rev. 2021;68:101343.
14

Burtscher J, Millet GP, Burtscher M. Does living at moderate altitudes in Austria affect mortality rates of various causes? An ecological study. BMJ Open. 2021;11(6):e048520.

15

Carmeliet P, Dor Y, Herbert JM, Fukumura D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshert E. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998;394(6692):485–90.

16

Carreau A, Hafny-Rahbi BEI, Matejuk A, Grillon C, Kieda C. Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med. 2011;15(6):1239–53.

17

Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, Capla JM, Galiano RD, Levine JP, Gurtner GC. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–64.

18

Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT. Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci U S A. 1998;95(20):11715–20.

19

Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem. 2000;275(33):25130–8.

20

Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW, Clifford SC, Maher ER, Pugh CW, Ratcliffe PJ, Maxwell PH. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel–Lindau tumor suppressor protein. J Biol Chem. 2000;275(33):25733–41.

21

Dang EV, Barbi J, Yang H-Y, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen H-R, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell. 2011;146(5):772–84.

22

Daut J, Maier-Rudolph W, von Beckerath N, Mehrke G, Günther K, Goedel-Meinen L. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science. 1990;247(4948):1341–4.

23

Dill DB, Adams WC. Maximal oxygen uptake at sea level and at 3,090-m altitude in high school champion runners. J Appl Physiol. 1971;30(6):854–9.

24

Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998;273(19):11619–24.

25

Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656–65.

26

Ema M, Taya S, Yokotani N, Sogawa K, Matsuda Y, Fujii-Kuriyama Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc Natl Acad Sci U S A. 1997;94(9):4273–8.

27

Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, Le Q-T, Giaccia AJ. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell. 2009;15(1):35–44.

28

Faeh D, Gutzwiller F, Bopp M, Swiss National Cohort Study Group. Lower mortality from coronary heart disease and stroke at higher altitudes in Switzerland. Circulation. 2009;120(6):495.

29

Faeh D, Moser A, Panczak R, Bopp M, Röösli M, Spoerri A, Swiss National Cohort Study Group. Independent at heart: persistent association of altitude with ischaemic heart disease mortality after consideration of climate, topography and built environment. J Epidemiol Community Health. 2016;70(8):798–806.

30

Fasanaro P, D'Alessandra Y, Stefano VD, Melchionna R, Romani S, Pompilio G, Capogrossi MC, Martelli F. MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem. 2008;283(23):15878–83.

31

Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996;16(9):4604–13.

32

Fukuda R, Hirota K, Fan F, Jung YD, Ellis LM, Semenza GL. Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem. 2002;277(41):38205–11.

33

Fukuda R, Zhang H, Kim J, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007;129(1):111–22.

34

Gemmill CL. Aviation physiology. Annu Rev Physiol. 1946;8:499–514.

35

Gerber HP, Condorelli F, Park J, Ferrara N. Differential transcriptional regulation of the two vascular endothelial growth factor receptor genes. Flt-1, but not Flk-1/KDR, is up-regulated by hypoxia. J Biol Chem. 1997;272(38):23659–67.

36

Girard O, Brocherie F, Millet GP. Effects of altitude/hypoxia on single- and multiple-sprint performance: a comprehensive review. Sports Med. 2017;47(10):1931–49.

37

Graeber TG, Peterson JF, Tsai M, Monica K, Fornace AJ, Giaccia AJ. Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol Cell Biol. 1994;14(9):6264–77.

38

Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe S, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996;379(6560):88–91.

39

Gustafsson MV, Zheng X, Pereira T, Gradin K, Jin S, Lundkvist J, Ruas JL, Poellinger L, Lendahl U, Bondesson M. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev Cell. 2005;9(5):617–28.

40

Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U, Schumacker PT. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 2005;1(6):401–8.

41

Guzy RD, Schumacker PT. Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol. 2006;91(5):807–19.

42

Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet. 1976;2(7996):1149–55.

43

Hackett PH, Roach RC. High-altitude illness. N Engl J Med. 2001;345(2):107–14.

44

Hagen T, Taylor CT, Lam F, Moncada S. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science. 2003;302(5652):1975–8.

45

Hewitson KS, McNeill LA, Riordan MV, Tian YM, Bullock AN, Welford RW, Elkins JM, Oldham NJ, Bhattacharya S, Gleadle JM. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002;277(29):26351–5.

46

Hirsila M, Koivunen P, Günzler V, Kivirikko KI, Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem. 2003;278(33):30772–80.

47

Hochachka PW. Defense strategies against hypoxia and hypothermia. Science. 1986;231(4735):234–41.

48

Hochachka PW, Buck LT, Doll CJ, Land SC. Unifying theory of hypoxia tolerance: molecular/metabolic defense and rescue mechanisms for surviving oxygen lack. Proc Natl Acad Sci U S A. 1996;93(18):9493–8.

49

Hockel M, Schlenger K, Aral B, Mitze M, Schaffer U, Vaupel P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 1996;56(19):4509–15.

50

Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol. 2003;23(24):9361–74.

51

Huang LE, Arany Z, Livingston DM, Bunn HF. Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem. 1996;271(50):32253–9.

52

Hudson CC, Liu M, Chiang GG, Otterness DM, Abraham RT. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002;22(20):7004–14.

53

Iliopoulos O, Levy AP, Jiang C, Kaelin WG, Goldberg MA. Negative regulation of hypoxia-inducible genes by the von Hippel–Lindau protein. Proc Natl Acad Sci U S A. 1996;93(20):10595–9.

54

Isaacs JS, Jung YJ, Mimnaugh EG, Martinez A, Cuttitta F, Neckers LM. Hsp90 regulates a von Hippel–Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem. 2002;277(33):29936–44.

55

Jiang BH, Rue E, Wang GL, Roe R, Semenza GL. Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem. 1996;271(30):17771–8.

56

Kallio PJ, Wilson WJ, O'Brien S, Makino Y, Poellinger L. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J Biol Chem. 1999;274(10):6519–25.

57

Keith B, Simon MC. Hypoxia-inducible factors, stem cells, and cancer. Cell. 2007;129(3):465–72.

58

Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab. 2006;3(3):177–85.

59

Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol. 2002;22(21):7405–16.

60

Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE, Sarkadi B, Sorrentino BP, Schuetz JD. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem. 2004;279(23):24218–25.

61

Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu CG, Croce CM, Negrini M, Calin GA, Ivan M. A microRNA signature of hypoxia. Mol Cell Biol. 2007;27(5):1859–67.

62

Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science. 2002;295(5556):858–61.

63

Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. Mol Cell Biol. 2001;21(12):3995–4004.

64

Lavoisier A. Mémoire sur la combustion en général. Mémoires de l’Académie des sciences. 1777;592.

65

Lee PJ, Jiang BH, Chin BY, Iyer NV, Alam J, Semenza GL, Choi AMK. Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem. 1997;272(9):5375–81.

66

Levine BD, Stray-Gundersen J. “Living high-training low”: effect of moderate-altitude acclimatization with low-altitude training on performance. J Appl Physiol. 1997;83(1):102–12.

67

Levy AP, Levy NS, Wegner S, Goldberg MA. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem. 1995;270(22):13333–40.

68

Levy NS, Chung S, Furneaux H, Levy AP. Hypoxic stabilization of vascular endothelial growth factor mRNA by the RNA-binding protein HuR. J Biol Chem. 1998;273(11):6417–23.

69

Levy AP, Levy NS, Goldberg MA. Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem. 1996;271(5):2746–53.

70

Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE, Hjelmeland AB, Rich JN. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell. 2009;15(6):501–13.

71

Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002;282(2):C227–41.

72

Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2):177–85.

73

Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet. 1981;1(8222):681–6.

74

Lundby C, Millet GP, Calbet JA, Bärtsch P, Subudhi AW. Does “altitude training” increase exercise performance in elite athletes? Br J Sports Med. 2012;46(11):792–5.

75

Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell. 2011;145(5):732–44.

76

Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010;40(2):294–309.

77

Mallet RT, Manukhina EB, Ruelas SS, Caffrey JL, Fred DH. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms and therapeutic potential. Am J Physiol Heart Circ Physiol. 2018;315(2):H216–32.

78

Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW, Ratcliffe PJ. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci U S A. 1997;94(15):8104–9.

79

Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 1999;399(6733):271–5.

80

Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio L. A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J Exp Med. 1995;182(6):1683–93.

81

Metallo CM, Gameiro PA, Bell EL, Mattaini KR, Yang J, Hiller K, Jewell CM, Johnson ZR, Irvine DJ, Guarente L, Kelleher JK, Vander Heiden MG, Iliopoulos O, Stephanopoulos G. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature. 2011;481(7381):380–4.

82

Millet GP, Girard O, Beard A, Brocherie F. Repeated sprint training in hypoxia—an innovative method. Deutsche Zeitschrift für Sportmedizin. 2019;70:115–22.

83

Moslehi J, Rathmell WK. The 2019 Nobel Prize honors fundamental discoveries in hypoxia response. J Clin Invest. 2020;130(1):4–6.

84

Mu J, Brozinick JT, Valladares O, Bucan M, Birnbaum MJ. A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle. Mol Cell. 2001;7(5):1085–94.

85

Mukhopadhyay D, Tsiokas L, Zhou XM, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature. 1995;375(6532):577–81.

86

Neonatal Inhaled Nitric Oxide Study G. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997;336(9):597–604.

87

Noman MZ, Saoussen K, Giacomo D, Philippe D. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–90.

88

Ohh M, Park CW, Ivan M, Hoffman MA, Kaelin WG. Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel–Lindau protein. Nat Cell Biol. 2000;2(7):423–7.

89

Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab. 2006;3(3):187–97.

90

Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci U S A. 2007;104(13):5431–6.

91

Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell. 2003;3(4):347–61.

92

Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature. 2006;441(7092):437–43.

93
Priestley J. Experiments and observations on different kinds of air. Printed for J. Johnson. 1775;72.
94

Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med. 2003;9(6):677–84.

95

Rankin EB, Giaccia AJ. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 2008;15(4):678–85.

96

Raval RR, Lau KW, Tran MGB, Sowter HM, Mandriota SJ, Li JL, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel–Lindau-associated renal cell carcinoma. Mol Cell Biol. 2005;25(13):5675–86.

97

Richalet JP. The scientific observatories on Mont Blanc. High Alt Med Biol. 2001;2(1):57–68.

98

Richalet JP. The invention of hypoxia. J Appl Physiol. 2021;130(5):1573–82.

99

Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008;453(7196):807–11.

100

Rubanyi GM, Vanhoutte PM. Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium. J Physiol. 1985;364:45–56.

101

Sahlgren C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci U S A. 2008;105(17):6392–7.

102

Salceda S, Caro J. Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem. 1997;272(36):22642–7.

103
Scheele C. d. Königl. Schwed. Acad. d. Wissenschaft. Mitgliedes, Chemische Abhandlung von der Luft und dem Feuer. Uppsala and Liepzig: Magnus Swederus; 1777.
104

Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med. 2003;198(9):1391–402.

105

Schmedtje JF Jr, YS Ji, Liu WL, DuBois RN, Runge MS. Hypoxia induces cyclooxygenase-2 via the NF-kappaB p65 transcription factor in human vascular endothelial cells. J Biol Chem. 1997;272(1):601–8.

106

Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci U S A. 1991;88(13):5680–4.

107

Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269(38):23757–63.

108

Semenza GL, Jiang BH, Leung SW, Passantino R, Concordet JP, Maire P, Giallongo A. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J Biol Chem. 1996;271(51):32529–37.

109

Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol. 1999;15:551–78.

110

Semenza GL. HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl Physiol. 2000;88(4):1474–80.

111

Semenza GL. HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell. 2001;107(1):1–3.

112

Semenza GL. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol. 2001;13(2):167–71.

113

Semenza GL. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med. 2001;7(8):345–50.

114

Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (Bethesda). 2009;24:97–106.

115

Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 2010;29(5):625–34.

116

Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399–408.

117

Semenza GL. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol Sci. 2012;33(4):207–14.

118

Shankaran S. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.

119

Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H, Tsujimoto Y. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature. 1995;374(6525):811–3.

120

Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992;359(6398):843–5.

121

Shweiki D, Neeman M, Itin A, Keshet E. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci U S A. 1995;92(3):768–72.

122

Simonson TS, Yang Y, Huff CD, Yun H, Qin G, Witherspoon DJ, Bai Z, Lorenzo FR, Xing J, Jorde LB, Prchal JT, Ge R. Genetic evidence for high-altitude adaptation in Tibet. Science. 2010;329(5987):72–5.

123

Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, Schneider JW, Zhang CC, Sadek HA. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell. 2010;7(3):380–90.

124

Somjen GG. Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev. 2001;81(3):1065–96.

125
Trio Wins Nobel for Hypoxia Discoveries. Cancer Discov. 2019;9(12):1636–7.
126

Ullah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem. 2006;281(14):9030–7.

127

Vanden Hoek TL, Becker LB, Shao Z, Li C, Schumacker PT. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem. 1998;273(29):18092–8.

128

Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39.

129

Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, Sobolewski A, Condliffe AM, Cowburn AS, Johnson N, Chilvers ER. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005;201(1):105–15.

130

Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A. 1995;92(12):5510–4.

131

Wang GL, Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A. 1993;90(9):4304–8.

132

Wang GL, Semenza GL. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem. 1993;268(29):21513–8.

133

Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270(3):1230–7.

134

West JB. 100th anniversary of the Anglo–American Pikes Peak expedition. High Alt Med Biol. 2011;12(3):189–90.

135

Wiesner S, Haufe S, Engeli S, Mutschler H, Haas U, Luft FC, Jordan J. Influences of normobaric hypoxia training on physical fitness and metabolic risk markers in overweight to obese subjects. Obesity (Silver Spring). 2010;18(1):116–20.

136

Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393–410.

137

Wise DR, Ward PS, Shay JES, Cross JR, Gruber JJ, Sachdeva UM, Platt JM, DeMatteo RG, Simon MC, Thompson CB. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of alpha-ketoglutarate to citrate to support cell growth and viability. Proc Natl Acad Sci U S A. 2011;108(49):19611–6.

138

Wouters BG, Koritzinsky M. Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nat Rev Cancer. 2008;8(11):851–64.

139

Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res. 2005;65(2):613–21.

140

Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, Ensrud KE, Ancoli-Israel S, Stone KL. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011;306(6):613–9.

141

Ye J, Gao Z, Yin J, He Q. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab. 2007;293(4):E1118–28.

142

Yi X, Liang Y, Huerta-Sanchez E, Jin X, Cuo ZX, Pool JE, Xu X, Jiang H, Vinckenbosch N, Korneliussen TS, Zheng H, Liu T, He W, Li K, Luo R, Nie X, Wu H, Zhao M, Cao H, Zou J, Shan Y, Li S, Yang Q, Asan, Ni P, Tian G, Xu J, Liu X, Jiang T, Wu R, Zhou G, Tang M, Qin J, Wang T, Feng S, Li G, Huasang, Luosang J, Wang W, Chen F, Wang Y, Zheng X, Li Z, Bianba Z, Yang G, Wang X, Tang S, Gao G, Chen Y, Luo Z, Gusang L, Cao Z, Zhang Q, Ouyang W, Ren X, Liang H, Zheng H, Huang Y, Li J, Bolund L, Kristiansen K, Li Y, Zhang Y, Zhang X, Li R, Li S, Yang H, Nielsen R, Wang J, Wang J. Sequencing of 50 human exomes reveals adaptation to high altitude. Science, 2010;329(5987):75–8.

143

Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell. 2009;5(3):237–41.

144

Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, Gonzalez FJ, Semenza GL. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 2008;283(16):10892–903.

145

Zhong H. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000;60(6):1541–5.

Journal of Science in Sport and Exercise
Pages 293-305
Cite this article:
Millet GP, Burtscher M, Burtscher J. Is Hypoxic/Altitude Training an Important Topic in the Field of Hypoxia?. Journal of Science in Sport and Exercise, 2022, 4(4): 293-305. https://doi.org/10.1007/s42978-021-00144-y

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Received: 16 August 2021
Accepted: 29 September 2021
Published: 09 December 2021
© The Author(s) 2021
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