Comparison of HIF-1⍺ and EPO Levels Before and After Exercise in Athletes Acclimatized to Low-Middle Altitude

Abstract

This study was conducted to examine the effect of acute exercise on HIF-1⍺ and EPO serum levels in well-trained male skiers adapted to low-medium altitude. The study was conducted with 15 male skiers with an average age of 20.33±1.91 years, average height of 170.93±10.62cm, and average body mass of 62.80±11.00kg. Bruce Treadmill test was performed to determine the participants' maximum oxygen consumption and to interpret their aerobic power levels. Determination of levels of selected blood cells, HIF-1α and EPO; Blood was taken from the participants at an altitude of 1000m, an exercise test was performed at the ski resort at an altitude of 2000m on the same day, blood was taken again 2 hours later, and blood was taken again the next morning, three times. Skiers who continued their normal training cycles were subjected to a single-repetition exercise protocol and the levels of relevant markers were determined with before and after blood tests. As a result, the highest level in selected blood parameters was reached at the last test (after 24 hours) (except WBC). It was observed that the difference between the tests was significant (p<0.05) in WBC, RBC, HGB, HCT parameters (except PLT). While the difference between the tests at the HIF-1α level was not significant (p>0.05), it was determined to be significant at the EPO level (p<0.05). In such studies, it is thought that sedentary-athlete comparison, chronic exercise tests and temporal follow-up spread over wider hours/days will contribute to the literature with more qualified results.

Keywords

• Hif-1 Alpha
• Epo
• Altitude
• Hypoxia
• Aerobic Exercise

Düşük-Orta İrtifaya Aklimatize Sporcularda Egzersiz Öncesi ve Sonrası HIF-1⍺ ve EPO Düzeylerinin Karşılaştırılması

Abstract

Bu çalışma, düşük-orta irtifaya uyum sağlamış, iyi antrenmanlı erkek kayakçılarda akut egzersizin HIF-1⍺ ve EPO serum düzeylerine etkisini incelemek amacıyla yapıldı. Çalışma, yaş ortalaması 20.33±1.91yıl, boy ortalaması 170.93±10.62cm, vücut kütle ortalaması 62.80±11.00kg olan 15 erkek kayakçı ile yapıldı. Katılımcıların, VO2max için Bruce treadmill testi yapıldı. Seçilmiş kan hücreleri, HIF-1α ve EPO düzeylerinin belirlenmesi; 1000m rakım düzeyinde katılımcılardan kan alımı, aynı gün içerisinde 2000m rakımlı kayak merkezinde egzersiz testi ve 2 saat sonrasında tekrar kan alımı, ertesi sabah yine kan alımı şeklinde üç tekrarlı olarak yapıldı. Normal antrenman döngülerine devam eden kayakçılar, tek tekrarlı egzersiz protokolüne tabi tutularak, öncesi-sonrası yapılan kan testleriyle, ilgili markerlerin düzeyi belirlendi. Sonuç olarak, seçilmiş kan parametrelerinde en yüksek düzeye son testte (24 saat sonra) ulaşıldı (WBC hariç). WBC, RBC, HGB, HCT parametrelerinde testler arası farkın anlamlı olduğu (p<0.05) görüldü (PLT hariç). HIF-1α düzeyinde testler arasındaki farkın anlamlı olmadığı (p>0.05) görülürken, EPO düzeyinde anlamlı olduğu (p<0.05) belirlendi. Bu tip çalışmalarda, sedanter-sporcu karşılaştırması, kronik egzersiz testlerinin yapılması ve zamansal takibin daha geniş saatlere/günlere yayılmasının daha nitelikli sonuçlarla literatüre katkı sağlayacağı düşünülmektedir.

Keywords

• Hif-1 Alfa
• Epo
• İrtifa
• Hipoksi
• Aerobik Egzersiz

References

1. Amaro-Gahete F.J., de-la-O, A., Jurado-Fasoli, L., Gutiérrez, Á., Ruiz, J.R. ve Castillo, M.J. (2019). Association of physical activity and fitness with S-Klotho plasma levels in middle-aged sedentary adults. the FIT-AGEING study. Maturitas, 123,25-31. DOI: 10.1016/j.maturitas.2019.02.001
2. Baygutalp, F., Buzdağlı, Y., Ozan, M., Koz, M., Kılıç Baygutalp, N. ve Atasever, G. (2021). Impacts of different intensities of exercise on inflammation and hypoxia markers in low altitude, BMC Sports Sci Med Rehabil. Nov 22;13(1):145. DOI: 10.1186/s13102-021-00375-0
3. Bruce, R.A., Kusumi, F. ve Hosmer, D. (1973): Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 85:546-551. DOI: 10.1016/0002-8703(73)90502-4
4. Budak, C., Uçan, İ., Dündar, S.T. ve Mertoğlu, C. (2023). Sstudy on vitamin d, cortisol and testosterone values in male skiers by seasonal cycles, The Online Journal of Recreation and Sports (TOJRAS), 12(3), 270-278.DOI: 10.22282/tojras.1275508
5. Chapman, R.F., Stray-Gundersen, J. ve Levine, B.D. (1998). Individual variation in response to altitude training. Journal of Applied Physiology 85, 1448-1456. DOI: 10.1152/jappl.1998.85.4.1448
6. Chavez, J.C., Baranova, O., Lin, J. ve Pichiule, P. (2006). The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J Neurosci, 26(37):9471-9481. DOI: 10.1523/JNEUROSCI.2838-06.2006
7. Chen, C.D., Podvin, S., Gillespie, E., Leeman, S.E. ve Abraham, C.R. (2007). Insulin stimulates the cleavage and release of the extra-cellular domain of Klotho by adaM10 and adaM17. procNatl Acad Sci USA,104:19796-801. DOI: 10.1073/pnas.0709805104
8. Czuba, M., Fidos-Czuba, O., Płoszczyca, K., Zając, A. ve Langfort, J. (2018). Comparison of the effect of intermittent hypoxic training vs. the live high, train low strategy on aerobic capacity and sports performance in cyclists in normoxia. Biol Sport. 35(1): 39–48. DOI: 10.5114/biolsport.2018.70750

9. Czuba, M., Maszczyk, A., Gerasimuk, D., Roczniok, R., Fidos-Czuba, O., Zając, A., Gołaś, A., Mostowik, A. ve Langfort, J. (2014). The effects of hypobaric hypoxia on erythropoiesis, maximal oxygen uptake and energy cost of exercise under normoxia in elite biathletes. J Sports Sci Med. Dec 1;13(4): 912-20.
10. Eltzschig, H.K. ve Carmeliet, P. (2011). Hypoxia and inflammation. N. Engl. J. Med. 364, 656–665. DOI: 10.1056/NEJMra0910283
11. Ericsson, K.A., Nandagopal, K. ve Roring, R.W. (2009). Toward a science of exceptional achievement: attaining superior performance through deliberate practice. Ann N Y Acad. Sci, 1172, 199–217. DOI: 10.1196/annals.1393.001
12. Foley, R.N. (2008). Erythropoietin: physiology and molecular mechanisms, Heart Fail Rev 13:405–414. DOI: 10.1007/s10741-008-9083-0
13. Foster, C., Jackson, A. S., Pollock, M. L., Taylor, M. M., Hare, J., Sennett, S. M., Rod, J. L., Sarwar, M. ve Schmidt, D. H. (1984) Generalized Equations For Predicting Functional Capacity From Treadmill Performance. American Heart Journal 107: 1229: 1234. DOI: 10.1016/0002-8703(84)90282-5
14. Girginer, F., Büyükyazı, G., Ulman, C., Doğru, Y., Taneli, F., Yıldız, R., Taş, M. ve Keskinoğlu, P. (2019). Comparison of Some Plasma InflammationMarkers in Elite Master Athletes, Recreational Athletes andSedentary Males. Türkiye Klinikleri J Med Sci, 39(2), (s. 202-11). DOI: 10.5336/medsci.2018-63235
15. Gruber, M., Hu, C.J., Johnson, R.S., Brown, E.J., Keith, B. ve Simon, M.C. (2007). Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci USA, 104(7):2301-2306. DOI: 10.1073/pnas.0608382104
16. Haase, V.H. (2013). Regulation of Erythropoiesis by Hypoxia-Inducible Factors. Blood Rev. 27, 41–53. DOI: 10.1016/j.blre.2012.12.003
17. Hawley, J.A., Lundby, C., Cotter, J.D. ve Burke, L.M. (2018). Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle, Cell Metabolism 27(5):962-976. DOI: 10.1016/j.cmet.2018.04.014
18. Hirota, K. ve Semenza, GL. (2006). Regulation of angiogenesis by hypoxia-inducible factor 1. Crit Rev Oncol Hematol, 59(19):15-26. DOI: 10.1016/j.critrevonc.2005.12.003
19. Hu, C.J., Wang, L.Y., Chodosh, L.A., Keith, B. ve Simon, M.C. (2003). Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol. Cell. Biol. 23, 9361–9374. DOI: 10.1128/MCB.23.24.9361-9374.2003
20. Kalinowski, L., Janaszak-Jasiecka, A., Siekierzycka, A., Bartoszewska, S., Wo´zniak, M., Lejnowski, D., Collawn, J.F. ve Bartoszewska, R. (2016) Posttranscriptional and transcriptional regulation of endothelial nitric-oxide synthase during hypoxia: the role ofmicroRNAs. Cell. Mol. Biol. Lett. 21, 16. DOI: 10.1186/s11658-016-0017-x
21. Keith, B., Johnson, R.S. ve Simon, M.C. (2011). HIF1a andHIF2a: sibling rivalry in hypoxic tumour growth and progression. Nat. Rev.Cancer, 12, 9–22. DOI: 10.1038/nrc3183
22. Koh, M.Y. ve Powis, G. (2012). Passing the button: the HIF swich. Trends in Biochemical Sciences; 37(9):364-372. DOI: 10.1016/j.tibs.2012.06.004
23. Li, J., Li, Y., Atakan, M.M., Kuang, J., Hu, Y., Bishop, D.J. ve Yan, X. (2020). The Molecular Adaptive Responses of Skeletal Muscle to High-Intensity Exercise/Training and Hypoxia, Antioxidants, 9(8):656. DOI: 10.3390/antiox9080656
24. McArdle, A., Pattwell, D., Vasilaki ,A., Griffiths, R.D. ve Jackson M.J. (2001). Contractile activity-induced oxidative stress: cellu-lar origin and adaptive responses. Am J Physiol Cell Physiol, 280:C621-7. DOI: 10.1152/ajpcell.2001.280.3.C621
25. Mostafidi, E., Moeen, A., Nasri, H., Ghorbani, Hagjo. ve A, Ardalan M. (2016). Serum klotho levels in trained athletes. Nephrourol Mon,8:e30245. DOI: 10.5812/numonthly.30245
26. Park, HY., Jung, WS., Kim, SW., Kim, J. ve Lim, K. (2022). Effects of Interval Training Under Hypoxia on Hematological Parameters, Hemodynamic Function, and Endurance Exercise Performance in Amateur Female Runners in Korea, Physiol, May 18; 13: 919008. DOI: 10.3389/fphys.2022.919008
27. Pedersen, L., Pedersen, S.M., Brasen, C.L. ve Rasmussen LM. (2013). Soluble serum Klotho levels in healthy subjects.comparison of two different immunoassays. Clin Biochem, 46:1079-83. DOI: 10.1016/j.clinbiochem.2013.05.046
28. Pramkratok, W., Songsupap, T. ve Yimlamai, T. (2022). Repeated sprint training under hypoxia improves aerobic performance and repeated sprint ability by enhancing muscle deoxygenation and markers of angiogenesis in rugby sevens, Eur J Appl Physiol, Mar;122(3):611-622. DOI: 10.1007/s00421-021-04861-8
29. Rankin, E.B., Biju, M.P., Liu, Q., Unger, T.L., Rha, J., Johnson, R.S., Simon, M.C., Keith, B ve Haase, V.H.(2007). Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest, 117(4):1068-1077. DOI: 10.1172/JCI30117
30. Saghiv MS, Ben-Sira D, Goldhammer E ve Sagiv M. (2019). Are s-klotho’s maximal concentrations dependent on exercise in-tensity and time in young adult males? J cardiol cardiovasc Med, 4:6-11. DOI: 10.29328/journal.jccm.1001033
31. Semenza, G.L. (1999). Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu. Rev. Cell Dev. Biol, 15, 551–578. DOI: 10.1146/annurev.cellbio.15.1.551
32. Semenza, G.L. (2001) HIF-1, O (2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus. Cell 107:1–3. DOI: 10.1016/s0092-8674(01)00518-9
33. Semenza, G.L., Nejfelt, M.K., Chi, S.M. ve Antonarakis, S.E. (1991). Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc. Natl. Acad. Sci. USA 88, 5680–5684. DOI: 10.1073/pnas.88.13.5680
34. Teti̇k Dündar, S., Akcan, İ.O, ve Ağgön, E. (2023a). Investigation of some physical parameters and aerobic–anaerobic power outcomes in mountain skiers. Research in Sport Education and Sciences, 25(1), 1-6.
35. Tetik Dündar, S., Kuzucu, M. ve Varol, S.R. (2023b). Effect of the aerobic power test performed at low-medium altitude on the myostatin, pgc-1 alpha and klotho levels. Gazz Med Ital-Arch Sci Med, 182:342-51.
36. Tomc, J. ve Debeljak, N. (2021). Molecular Insights into the Oxygen-Sensing Pathway and Erythropoietin Expression Regulation in Erythropoiesis, Int. J. Mol. Sci. 22, 7074. DOI: 10.3390/ijms22137074
37. Tucker, R. ve Collins, M. (2012). What makes champions? A review of the relative contribution of genes and training to sporting success. Br. J. Sports Med. 46, 555–561. DOI: 10.1136/bjsports-2011-090548
38. Van Thienen, R., Masschelein, E., D’Hulst, G., Thomis, M. ve Hespel, P. (2016). Twin Resemblance in Muscle HIF-1alpha Responses to Hypoxia and Exercise. Front. Physiol. 7, 676. DOI: 10.3389/fphys.2016.00676
39. Wang, G.L. ve Semenza, G.L. (1993). General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc. Natl. Acad. Sci. USA 90, 4304–4308. DOI: 10.1073/pnas.90.9.4304
40. Wojan, F., Stray-Gundersen, S., Massoudian, S.D. ve Lalande, S. (2023). Brief exposure to intermittent hypoxia increases erythropoietin levels in older adults, J Appl Physiol. 1;135 (1): 88-93. DOI: 10.1152/japplphysiol.00172.2023
41. Yatsutani, H., Mori, H., Ito, H., Hayashi, N., Girard, O. ve Goto, K. (2020). Endocrine and Metabolic Responses to Endurance Exercise Under Hot and Hypoxic Conditions. Front. Physiol. 11:932. DOI: 10.3389/fphys.2020.00932
42. Żebrowska, A., Jastrzębski, D., Sadowska-Krępa, E., Sikora, M. ve Di Giulio, C. (2019). Comparison of the Effectiveness of High-Intensity Interval Training in Hypoxia and Normoxia in Healthy Male Volunteers: A Pilot Study, Biomed Res Int, Sep 22; 7315714. DOI: 10.1155/2019/7315714
43. Zhu, H. ve Bunn, H.F. (2001). Signal transduction: how do cells sense oxygen? Science 292:449–451. DOI: 10.1126/science.1060849