Mechanisms and triggers of adaptation to hypoxia

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

It is believed that hypoxia-induced factor (HIF1) is the key mediator of oxygen metabolism. It was first identified as a transcription factor activated in cells and tissues by lowering the partial pressure of oxygen (O2). The HIF1 activator spectrum includes both external factors – hypoxia, psycho-emotional stress and in ternal factors and varies from hormones to iron chelators. This review is dedicated to the molecular mechanisms of HIF1 activation, some of its natural activators HIF1, the potential for which is due to the low level of toxicity and the reduced likelihood of undesirable side effects. In turn, this opens up new options to treat diseases associated with local and general ischemia and hypoxia, the possibilities of their prophylactic use for researchers and clinicians in order to reduce the degree of damage in the event of an unforeseen condition of acute injurious to organs and tissues by hypoxia and reperfusion after it.

About the authors

Andrey V. Lyubimov

Institute of Experimental Medicine; S.M. Kirov Military Medical Academy

Email: lyubimov_av@mail.ru
ORCID iD: 0000-0001-9829-4681

PhD (Med.)

Russian Federation, 12 Academika Pavlova str., 197376, Saint Petersburg; 6, Acad. Lebedeva street, Saint Petersburg, 194044

Dmitriy V. Cherkashin

Institute of Experimental Medicine; S.M. Kirov Military Medical Academy

Email: cherkashin-dmitr@mail.ru
ORCID iD: 0000-0003-1363-6860
SPIN-code: 2781-9507

Doctor of Medical Sciences

Russian Federation, 12, Acad. Pavlov Street, Saint-Petersburg, 197376; 6, Acad. Lebedeva street, Saint Petersburg, 194044

Semen V. Efimov

Military Medical Academy. S. M. Kirov

Author for correspondence.
Email: sve03@rambler.ru

PhD, Cand. Sci. (Med.)

Russian Federation, 6, Acad. Lebedeva street, Saint Petersburg, 194044

Andrey E. Alanichev

Military Medical Academy. S. M. Kirov

Email: alanichevae80@mail.ru
ORCID iD: 0000-0002-4135-5815

PhD, Cand. Sci. (Med.)

Russian Federation, 6, Acad. Lebedeva street, Saint Petersburg, 194044

Valeriy S. Ivanov

Military Medical Academy. S. M. Kirov

Email: ivanovmed84@mail.ru
SPIN-code: 1965-4741

Senior Clinic Resident

Russian Federation, 6, Acad. Lebedeva street, Saint Petersburg, 194044

Gennadiy G. Kutelev

Military Medical Academy. S. M. Kirov

Email: gena08@yandex.ru
ORCID iD: 0000-0002-6489-9938
SPIN-code: 5139-8511

PhD, Cand. Sci. (Med.)

Russian Federation, 6, Acad. Lebedeva street, Saint Petersburg, 194044

References

  1. Huang LE, Bunn HF. Hypoxia-inducible factor and its biomedical relevance. J Biol Chem. 2003;278(22):19575–19578. doi: 10.1074/jbc.R200030200
  2. Poellinger L, Johnson RS. HIF1 and hypoxic response: the plot thickens. Curr Opin Genet Dev. 2004;14(1):81–85. doi: 10.1016/j.gde.2003.12.006
  3. Semenza GL. Targeting HIF1 for cancer therapy. Nat Rev Cancer. 2003;3:721–732. doi: 10.1038/nrc1187
  4. 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 USA. 1995;92(12):5510–5514. doi: 10.1073/pnas.92.12.5510
  5. Dames SA, Martinez-Yamout M, De Guzman RN, et al. Structural basis for HIF1α/CBP recognition in the cellular hypoxic response. Proc Natl Acad Sci USA. 2002;99(8):5271–5276. doi: 10.1073/pnas.082121399
  6. Freedman SJ, Sun ZY, Poy F, et al. Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α. Proc Natl Acad Sci USA. 2002;99(8):5367–5372. doi: 10.1073/pnas.082117899
  7. Hewitson KS, McNeill LA, Riordan MV, et al. 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):26351–26355. doi: 10.1074/jbc.C200273200
  8. Lando D, Peet DJ, Gorman JJ, et al. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002;16:1466–1471. doi: 10.1101/gad.991402
  9. Lando D, Peet DJ, Whelan DA, et al. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science. 2002;295(5556):858–861. doi: 10.1126/science.1068592
  10. Lin SC, Liao WL, Lee JC, Tsai SJ. Hypoxia-regulated gene network in drug resistance and cancer progression. Exp Biol Med (Maywood). 2014;239(7):779–792. doi: 10.1177/1535370214532755
  11. Mahon PC, Hirota K, Semenza GL. FIH-1: a novel protein that interacts with HIF1α and VHL to mediate repression of HIF1 transcriptional activity. Genes Dev. 2001;15:2675–2686. doi: 10.1101/gad.924501
  12. McNeill LA, Hewitson KS, Claridge TD, et al. Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. Biochem J. 2002;367(3):571–575. doi: 10.1042/BJ20021162
  13. Singh D, Arora R, Kaur P, et al. Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer. Cell Biosci. 2017;7:62. doi: 10.1186/s13578-017-0190-2
  14. Jin P, Kang J, Lee MK, Park JW. Ferritin heavy chain controls the HIF-driven hypoxic response by activating the asparaginylhydroxylase FIH. Biochem Biophys Res Commun. 2018;499(3):475–481. doi: 10.1016/j.bbrc.2018.03.173
  15. Pugh CW. Modulation of the Hypoxic Response. Adv Exp Med Biol. 2016;903:259–271. doi: 10.1007/978-1-4899-7678-9_18
  16. Wang V, Davis DA, Yarchoan R. Identification of functional hypoxia inducible factor response elements in the human lysyl oxidase gene promoter. Biochem Biophys Res Commun. 2017;490(2):480–485. doi: 10.1016/j.bbrc.2017.06.066
  17. Brahimi-Horn C, Mazure N, Pouyssegur J. Signalling via the hypoxia-inducible factor-1α requires multiple posttranslational modifications. Cell Signal. 2005;17(1):1–9. doi: 10.1016/j.cellsig.2004.04.010
  18. Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993;82(12):3610–3615. doi: 10.1182/blood.V82.12.3610.3610
  19. Li L, Yin X, Ma N, et al. Desferrioxamin regulates HIF1 alpha expression in neonatal rat brain after hypoxia-ischemia. Am J Transl Res. 2014;6(4):377–383.
  20. AHFS Drug Information 2004. McEvoy, GK., editor. Bethesda: American Society of Health-System Pharmacists, Inc. American Hospital Formulary Service; 2004. P. 2870–2873.
  21. Gobin J, Moore CH, Reeve JR Jr, et al. Iron acquisition by Mycobacterium tuberculosis: isolation and characterization of a family of iron-binding exochelins. Proc Natl Acad Sci USA. 1995;92(11):5189–5193. doi: 10.1073/pnas.92.11.5189
  22. Chong TW, Horwitz LD, Moore JW, et al. A mycobacterial iron chelator, desferri-exochelin, induces hypoxia-inducible factors 1 and 2, NIP3, and vascular endothelial growth factor in cancer cell lines. Cancer Res. 2002;62:6924–6927.
  23. Shen T, Huang S. Repositioning the Old Fungicide Ciclopirox for New Medical Uses. Curr Pharm Des. 2016;22(28):4443–4450. doi: 10.2174/1381612822666160530151209
  24. Wanner RM, Spielmann P, Stroka DM, et al. Epolones induce erythropoietin expression via hypoxia-inducible factor-1α activation. Blood. 2000;96(4):1558–1565. doi: 10.1182/blood.V96.4.1558
  25. Linden T, Katschinski DM, Eckhardt K, et al. The antimycotic ciclopirox olamine induces HIF1α stability, VEGF expression, and angiogenesis. FASEB J. 2003;17(6):761–763. doi: 10.1096/fj.02-0586fje
  26. Schnitzer SE, Schmid T, Zhou J, et al. Inhibition of GSK3beta by indirubins restores HIF1alpha accumulation under prolonged periods of hypoxia / anoxia. FEBS Lett. 2005;579(2):529–533. doi: 10.1016/j.febslet.2004.12.023
  27. Cheng YC, Liou JP, Kuo CC, et al. MPT0B098, a novel microtubule inhibitor that destabilizes the hypoxia-inducible factor-1α mRNA through decreasing nuclear-cytoplasmic translocation of RNA-binding protein HuR. Mol Cancer Ther. 2013;12(7):1202–1212. doi: 10.1158/1535-7163.MCT-12-0778
  28. Jung YJ, Isaacs JS, Lee S, et al. Microtubule disruption utilizes an NFκB-dependent pathway to stabilize HIF1α protein. J Biol Chem 2003;278(9):7445–7452. doi: 10.1074/jbc.M209804200
  29. Shen J, Zhang JH, Xiao H, et al. Mitochondria are transported along microtubules in membrane nanotubes to rescue distressed cardiomyocytes from apoptosis. Cell Death Dis. 2018;9(2):81. doi: 10.1038/s41419-017-0145-x
  30. Zhou X, Xu Z, Li A, et al. Double-sides sticking mechanism of vinblastine interacting with α, β-tubulin to get activity against cancer cells. J Biomol Struct Dyn. 2019;37(15):4080–4091. doi: 10.1080/07391102.2018.1539412
  31. Guo C, Wang L, Jiang B, Shi D. Bromophenol curcumin analog BCA-5 exerts an antiangiogenic effect through the HIF1α/VEGF/Akt signaling pathway in human umbilical vein endothelial cells. Anticancer Drugs. 2018;29(10):965–974. doi: 10.1097/CAD.0000000000000671
  32. Mabjeesh NJ, Willard MT, Harris WB, et al. Dibenzoylmethane, a natural dietary compound, induces HIF1α and increases expression of VEGF. Biochem Biophys Res Commun. 2003;303(1):279–286. doi: 10.1016/s0006-291x(03)00336-x
  33. Wilson WJ, Poellinger L. The dietary flavonoid quercetin modulates HIF1α activity in endothelial cells. Biochem Biophys Res Commun. 2002;293(1):446–450. doi: 10.1016/S0006-291X(02)00244-9
  34. Welford RW, Schlemminger I, McNeill LA, et al. The selectivity and inhibition of AlkB. J Biol Chem. 2003;278(12):10157–10161. doi: 10.1074/jbc.M211058200
  35. Zhou YD, Kim YP, Li XC, et al Hypoxia-inducible factor-1 activation by (–)-epicatechin gallate: potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J Nat Prod. 2004;67:2063–2069. doi: 10.1021/np040140c
  36. Hong J, Lu H, Meng X, et al. Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (–)-epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells. Cancer Res. 2002;62:7241–7246.
  37. Demeule M, Michaud-Levesque J, Annabi B, et al. Green tea catechins as novel antitumor and antiangiogenic compounds. Curr Med Chem Anti-Canc Agents. 2002;2(4):441–463. doi: 10.2174/1568011023353930
  38. Burnley-Hall N, Willis G, Davis J, et al. Nitrite-derived nitric oxide reduces hypoxia-inducible factor 1α-mediated extracellular vesicle production by endothelial cells. Nitric Oxide. 2017;63:1–12. doi: 10.1016/j.niox.2016.12.005
  39. Huang LE, Willmore WG, Gu J, et al. Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. Implications for oxygen sensing and signaling. J Biol Chem. 1999;274(13):9038–9044. doi: 10.1074/jbc.274.13.9038
  40. La Padula PH, Etchegoyen M, Czerniczyniec A, et al. Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide. Nitric Oxide. 2018;73:52–59. doi: 10.1016/j.niox.2017.12.007
  41. Liu Y, Christou H, Morita T, et al. Carbon monoxide and nitric oxide suppress the hypoxic induction of vascular endothelial growth factor gene via the 5’ enhancer. J Biol Chem. 1998;273(24):15257–15262. doi: 10.1074/jbc.273.24.15257
  42. Sogawa K, Numayama-Tsuruta K, Ema M, et al. Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia. Proc Natl Acad Sci USA. 1998;95(13):7368–7373. doi: 10.1073/pnas.95.13.7368
  43. Vetrovoy O, Sarieva K, Galkina O, et al. Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain. Neurochem Res. 2019;44:1425–1436. doi: 10.1007/s11064-018-2681-x
  44. Kimura H, Weisz A, Kurashima Y, et al. Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide. Blood. 2000;95(1):189–197. doi: 10.1182/blood.V95.1.189
  45. Arandarcikaite O, Jokubka R, Borutaite V. Neuroprotective effects of nitric oxide donor NOC-18 against brain ischemia-induced mitochondrial damages: role of PKG and PKC. Neurosci Lett. 2015;586:65–70. doi: 10.1016/j.neulet.2014.09.012
  46. Palmer LA, Gaston B, Johns RA. Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides. Mol Pharmacol. 2000;58(6):1197–1203. doi: 10.1124/mol.58.6.1197
  47. Yang C, Hwang HH, Jeong S, et al. Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles. Int J Nanomedicine. 2018;13:6517–6530. doi: 10.2147/IJN.S174989
  48. Sumbayev VV, Budde A, Zhou J, Brune B. HIF1α protein as a target for S-nitrosation. FEBS Lett. 2003;535(1–3):106–112. doi: 10.1016/s0014-5793(02)03887-5
  49. Yasinska IM, Sumbayev VV. S-nitrosation of Cys-800 of HIF1α protein activates its interaction with p300 and stimulates its transcriptional activity. FEBS Lett. 2003;549(1–3):105–109. doi: 10.1016/s0014-5793(03)00807-x
  50. Frise MC, Cheng HY, Nickol AH, et al. Clinical iron deficiency disturbs normal human responses to hypoxia. J Clin Invest. 2016;126(6):2139–2150. doi: 10.1172/JCI85715
  51. Shah YM, Xie L. Hypoxia-inducible factors link iron homeostasis and erythropoiesis. Gastroenterology. 2014;146(3):630–642. doi: 10.1053/j.gastro.2013.12.031
  52. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol. 2004;5:343–354. doi: 10.1038/nrm1366
  53. Thomas DD, Espey MG, Ridnour LA, et al. Hypoxic inducible factor 1α, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci USA. 2004;101(24):8894–8899. doi: 10.1073/pnas.0400453101
  54. Mukundan H, Kanagy NL, Resta TC. 17-β estradiol attenuates hypoxic induction of HIF1α and erythropoietin in Hep3B cells. J Cardiovasc Pharmacol. 2004;44(1):93–100. doi: 10.1097/00005344-200407000-00013
  55. Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem. 2002;277(26):23111–23115. doi: 10.1074/jbc.M202487200
  56. Wang GL, Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA. 1993;90(9):4304–4308. doi: 10.1073/pnas.90.9.4304
  57. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem. 1995;270(3):1230–1237. doi: 10.1074/jbc.270.3.1230
  58. Muñoz-Sánchez J, Chánez-Cárdenas ME. The use of cobalt chloride as a chemical hypoxia model. J Appl Toxicol. 2018;39(4):556–570. doi: 10.1002/jat.3749
  59. Luczak MW, Zhitkovich A. Nickel-induced HIF1α promotes growth arrest and senescence in normal human cells but lacks toxic effects in transformed cells. Toxicol Appl Pharmacol. 2017;331:94–100. doi: 10.1016/j.taap.2017.05.029
  60. Salnikow K, An WG, Melillo G, et al. Nickel-induced transformation shifts the balance between HIF1 and p53 transcription factors. Carcinogenesis. 1999;20(9):1819–1823. doi: 10.1093/carcin/20.9.1819
  61. Salnikow K, Blagosklonny MV, Ryan H, et al. Carcinogenic nickel induces genes involved with hypoxic stress. Cancer Res. 2000;60:38–41.
  62. Kim D, Dai J, Park YH, et al. Activation of Epidermal Growth Factor Receptor/p38/Hypoxia-inducible Factor-1α Is Pivotal for Angiogenesis and Tumorigenesis of Malignantly Transformed Cells Induced by Hexavalent Chromium. J Biol Chem. 2016;291(31):16271–16281. doi: 10.1074/jbc.M116.715797
  63. Gao N, Jiang BH, Leonard SS, et al. p38 Signaling-mediated hypoxia-inducible factor 1α and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells. J Biol Chem. 2002;277(47):45041–45048. doi: 10.1074/jbc.M202775200
  64. Agani F, Semenza GL. Mersalyl is a novel inducer of vascular endothelial growth factor gene expression and hypoxia-inducible factor 1 activity. Mol Pharmacol. 1998;54(5):749–754. doi: 10.1124/mol.54.5.749
  65. Salnikow K, Donald SP, Bruick RK, et al. Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress. J Biol Chem. 2004;279(39):40337–40344. doi: 10.1074/jbc.M403057200
  66. Wu Z, Zhang W, Kang YJ. Copper affects the binding of HIF1α to the critical motifs of its target genes. Metallomics. 2019;11(2):429–438. doi: 10.1039/c8mt00280k
  67. Zelzer E, Levy Y, Kahana C, et al. Insulin induces transcription of target genes through the hypoxia-inducible factor HIF1α/ARNT. EMBO J. 1998;17(17):5085–5094. doi: 10.1093/emboj/17.17.5085
  68. Feldser D, Agani F, Iyer NV, et al. Reciprocal positive regulation of hypoxia-inducible factor 1α and insulin-like growth factor 2. Cancer Res. 1999;59:3915–3918.
  69. Cherkashin DV, Lyubimov AV. The molecular marker of the preconditioning phenomenon HIF1α is a new pathway for early detection of visceral hypoxic conditions. Therapeutic archive. 2020;92(4):121–126. (In Russ.) doi: 10.26442/00403660.2020.04.000473
  70. Lyubimov AV, Ivanov AO, Bezkishkii EN, et al. Assessment of the effect of long-term continuous stay in the artificial hypoxic gas-air environment at normal atmospheric pressure on the functional state of the cardiovascular system. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(3):47–53. (In Russ.) doi: 10.17816/RCF16347-53
  71. Mabjeesh NJ, Post DE, Willard MT, et al. Geldanamycin induces degradation of hypoxia-inducible factor 1α protein via the proteosome pathway in prostate cancer cells. Cancer Res. 2002;62:2478–2482.

Copyright (c) 2021 Lyubimov A.V., Cherkashin D.V., Efimov S.V., Alanichev A.E., Ivanov V.S., Kutelev G.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».