The role of the hypoxia signaling pathway in cellular adaptation to hypoxia
The review presents an analysis of scientific publications in recent years devoted to the study on the cellular-molecular mechanism of cellular adaptation to hypoxia. In many respiratory diseases (chronic obstructive pulmonary disease, chronic respiratory failure, etc.), the balance between the cells’ need for oxygen and its delivery is disrupted. It complicates the course of the diseases and is a potential factor in their progression. The microenvironment in the inflammatory areas becomes hypoxic (so-called inflammatory hypoxia). The formation of long-term adaptation to pathological hypoxia is associated with the expression of a specific hypoxia-induced factor (HIF). It serves as a transcription activator for more than 300 genes and is a key regulator of various cellular and systemic responses to hypoxia, including angiogenesis, cell proliferation, cellular migration, regeneration, antigen presentation, cytokine and antimicrobial peptide production, phagocytosis, apoptosis, and cellular metabolic reprogramming. The article also considers the complex cross-interaction between HIF signaling and the nuclear transcription factor κB — NF-κB) signaling pathway (one of the main regulators of inflammation and immune responses). Possible therapeutic methods for controlling inflammation and immune-related diseases based on the principle of regulating the HIF signaling pathway are discussed.
Keywords: respiratory diseases, hypoxia, hypoxia-induced factor, adaptation, inflammation, immunity, targeted therapy.
For citation: Titova O.N., Kuzubova N.A., Lebedeva E.S. The role of the hypoxia signaling pathway in cellular adaptation to hypoxia. Russian Medical Review. 2020;4(4) [Epub ahead of print]. DOI: 10.32364/2587-6821-2020-4-4.
DOI: 10.32364/2587-6821-2020-4-4
About authors:
Olga N. Titova — MD, PhD, Professor, Director; ORCID iD 0000-0003-4678-3904;
Natalia A. Kuzubova — MD, PhD, Deputy Research Officer; ORCID iD 0000-0002-1166-9717;
Elena S. Lebedeva — MD, PhD, Leading Researcher; ORCID iD 0000-0001-6887-0166.
National Research Institute of Pulmonology of the Pavlov First Saint Petersburg State Medical University: 6/8
ul. L. Tolstogo, bld. 44, Saint-Petersburg, 197022, Russian Federation.
Contact information: Natalia A. Kuzubova e-mail: kuzubova@mail.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interest. Received 19.03.2020.
References
1. Eltzschig H.K., Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011;364(7):656–665. DOI: 10.1056/NEJMra0910283.
2. Colgan S.P., Campbell E.L., Kominsky D.J. Hypoxia and mucosal inflammation. Ann Rev Pathol. 2016;11:77–100. DOI: 10.1146/annurev-pathol-012615-044231.
3. Cummins E.P., Keogh C.E., Crean D., Taylor C.T. The role of HIF in immunity and inflammation. Mol Aspects Med. 2016;47–48:24–34. DOI: 10.1016/j.mam.2015.12.004.
4. Taylor C.T., Doherty G., Fallon P.G., Cummins E.P. Hypoxia-dependent regulation of inflammatory pathways in immune cells. J Clin Invest. 2016;126(10):3716–3724. DOI: 10.1172/JCI84433.
5. Taylor C.T., Colgan S.P. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol. 2017;17(12):774–785. DOI: 10.1038/nri.2017.103.
6. Biddlestone J., Bandarra D., Rocha S. The role of hypoxia in inflammatory disease (review). Int J Mol Med. 2015;35(4):859–869. DOI: 10.3892/ijmm.2015.2079.
7. Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399–408. DOI: 10.1016/j.cell.2012.01.021.
8. Ratcliffe P.J. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. J Physiol. 2013;591(8):2027–2042. DOI: 10.1113/jphysiol.2013.251470.
9. Лукьянова Л.Д., Кирова Ю.И., Сукоян Г.В. Сигнальные механизмы адаптации к гипоксии и их роль в системной регуляции. Биологические мембраны. 2012;29(4):238–252. [Lukyanova L.D., Kirova Yu.I., Sukoyan G.V. Signaling mechanisms of adaptation to hypoxia and its role in systemic regulation. Biologicheskie membrany. 2012;29(4): 238–252 (in Russ.)].
10. Moniz S., Biddlestone J., Rocha S. Grow2: the HIF system, energy homeostasis and the cell cycle. Histol Histopathol. 2014;29(5):589–600. DOI: 10.14670/HH-29.10.589.
11. Zhang P., Yao Q., Lu L. et al. Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia. Cell Rep. 2014;6(6):1110–1121. DOI: 10.1016/j.celrep.2014.02.011.
12. Duan C. Hypoxia-inducible factor 3 biology: complexities and emerging themes. Am. J. Physiol. Cell Physiol. 2016;310(4): C260–269. DOI: 10.1152/ajpcell.00315.2015.
13. Kaelin W.G., Ratcliffe P.J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell. 2008;30(4):393–402. DOI: 10.1016/j.molcel.2008.04.009.
14. Krzywinska E., Stockmann C. Hypoxia, metabolism and immune cell function. Biomedicines. 2018;6(2):56. DOI: 10.3390/biomedicines6020056.
13. Dengler V.L., Galbraith M., Espinosa J.M. Transcriptional regulation by hypoxia inducible factors. Crit Rev. Biochem. Mol. Biol. 2014;49(1):1–15. DOI: 10.3109/10409238.2013.838205.
16. Lenihan C.R., Taylor C.T. The impact of hypoxia on cell death pathways. Biochem Soc Trans. 2013;41(2):657–663. DOI: 10.1042/BST20120345.
17. D’Ignazio L., Bandarra D., Rocha S. NF-κB and HIF crosstalk in immune responses. FEBS J. 2016;283(3):413–424. DOI: 10.1111/febs.13578.
18. Hoenderdos K., Lodge K.M., Hirs R.A. et al. Hypoxia upregulates neutrophil degranulation and potential for tissue injury. Thorax. 2016;71(11):1030–1038. DOI: 10.1136/thoraxjnl-2015-207604.
19. Polke M., Seiler F., Lepper P.M. et al. Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells. Innate Immun. 2017;23(4):373–380. DOI: 10.1177/1753425917698032.
20. Ito Y., Ahmad A., Kewley E., Mason R.J. Hypoxia-inducible factor regulates expression of surfactant protein in alveolar type II cells in vitro. Am J Respir Cell Mol Biol. 2011;45(5):938–945. DOI: 10.1165/rcmb.2011-0052OC.
21. Bandarra D., Biddlestone J., Mudie S. et al. HIF-1 alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals. Dis Model Mech. 2015;8(2):169–181. DOI: 10.1242/dmm.017285. 22. Scholz C.C., Taylor C.T. Hydroxylase-dependent regulation of the NF-κB pathway. Biol Chem. 2013;394(4):479–493. DOI: 10.1515/hsz-2012-0338.
23. Schuliga M. NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 2015;5(3):1266–1283. DOI: 10.3390/biom5031266.
24. Титова О.Н., Кузубова Н.А., Лебедева Е.С. и др. Противовоспалительный и регенеративный эффект подавления гипоксийного сигналинга на модели хронической обструктивной болезни легких. Пульмонология. 2018;28(2):169–176. [Titova O.N., Kuzubova O.N., Lebedeva E.S. et al. Anti-inflammatory and regenerative effects of hypoxic signaling inhibition in a model of COPD. Russian Pulmonology Journal. 2018;28(2):169–176 (in Russ.)]. DOI:10.18093/0869-0189-2018-28-2-169-176].
25. Tao J.H., Barbi J., Pan F. Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the theme: Cellular responses to hypoxia. Am J Physiol Cell Physiol. 2015;309(9):580–589. DOI: 10.1152/ajpcell.00204.2015.
26. Corcoran S.E., O’Neill L.A. HIF1α and metabolic reprogramming in inflammation. J Clin Invest. 2016;126(10):3699–3707. DOI: 10.1172/JCI84431.
27. Золотухин П.В., Беланова А.А., Празднова Е.В. и др. Митохондрии как сигнальный узел и мишень для отключения феноптоза. Биохимия. 2016;81(4):465–475. [Zolotuhin P.V., Belanova A.A., Prazdnova E.V. et al. Mitochondria as a signaling hub and target for phenoptosis shutdown, Biochemistry (Moscow). 2016;81(4):465–475 (in Russ.)].
28. Briston T., Stephen J.M., Thomas L.W. et al. VHL-mediated regulation of CHCHD4 and mitochondrial function. Front Oncol. 2018;8:388. DOI: 10.3389/fonc.2018.00388.
29. O’Neill L.A., Kishton R.J., Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16(9):553–565. DOI: 10.1038/nri.2016.70.
30. Halligan D.N., Murphy S.J., Taylor C.T. The hypoxia-inducible factor (HIF) couples immunity with metabolism. Semin Immunol. 2016;28(5):469–477. DOI: 10.1016/j.smim.2016.09.004.
31. Harris A.J., Thompson A.R., Whyte M.K., Walmsley S.R. HIF-mediated innate immune responses: cell signaling and therapeutic implications. Hypoxia (Auckl). 2014;2:47–58. DOI: 10.2147/HP.S50269.
32. Lin N., Simon M.C. Hypoxia-inducible factors: key regulators of myeloid cells during inflammation. J Clin Invest. 2016;126(10):3661–3671. DOI: 10.1172/JCI84426.
33. Hammami A., Charpentier T., Smans M., Stäger S. IRF-5-mediated inflammation limits CD8+ T Cell expansion by inducing HIF-1α and impairing dendritic cell functions during Leishmania infection. PLoS Pathog. 2015;11(6): e1004938. DOI: 10.1371/journal.ppat.1004938.
34. Mascanfroni I.D., Takenaka M.C., Yeste A. et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α Nat. Med. 2015;21(6):638–646. DOI: 10.1038/nm.3868.
35. Tyrakis P.A., Palazon A., Macias D. et al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016;540(7632):236–241. DOI: 10.1038/nature20165.
36. Phan A.T., Doedens A.L., Palazon A. et al. Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection. Immunity. 2016;45(5):1024–1037. DOI: 10.1016/j.immuni.2016.10.017.
37. Palazon A., Tyrakis P.A., Macias D. et al. An HIF-1α/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell. 2017;32(5):669–683.e5. DOI: 10.1016/j.ccell.2017.10.003.
38. Cho S.H., Raybuck A.L., Stengel K. et al. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system. Nature. 2016;537(7619):234–238. DOI: 10.1038/nature19334.
39. Crotty Alexander L.E., Akong-Moore K., Feldstein S. et al. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function. J Mol Med. 2013;91(5):637–644. DOI: 10.1007/s00109-012-0986-9.
40. Loftus R.M., Finlay D.K. Immunometabolism: Cellular metabolism turns immune regulator. J Biol Chem. 2016;291(1):1–10. DOI: 10.1074/jbc.R115.693903.
41. Branitzki-Heinemann K., Möllerherm H., Völlger L. et al. Formation of neutrophil extracellular traps under low oxygen level. Front. Immunol. 2016;7:518. DOI: 10.3389/fimmu.2016.00518.
42. Möllerherm H., von Köckritz-Blickwede M., Branitzki-Heinemann K. Antimicrobial activity of mast cells: Role and relevance of extracellular DNA traps. Front. Immunol. 2016;7:265. DOI: 10.3389/fimmu.2016.00265.
43. Diebold L., Chandel N.S. Mitochondrial ROS regulation of proliferating cells. Free Radic Biol Med. 2016;100:86–93. DOI: 10.1016/j.freeradbiomed.2016.04.198.
44. Thomas L.W., Ashcroft M. Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria. Cell Mol. Life Sci. 2019;76(9):1759–1777. DOI: 10.1007/s00018-019-03039-y.
45. Singh C.K., Chhabra G., Ndiaye M.A. et al. The role of sirtuins in antioxidant and redox signaling. Antioxid. Redox Signal. 2018;28(8):643–661. DOI: 10.1089/ars.2017.7290.
46. Ivan M., Kaelin W.G., Jr. The EGLN-HIF O2-sensing system: multiple inputs and feedbacks. Mol Cell. 2017;66(6):772–779. DOI: 10.1016/j.molcel.2017.06.002.
47. Fasano C., Disciglio V., Bertora S. et al. FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response. Cells. 2019;8(9): pii: E1110. DOI: 10.3390/cells8091110.
48. Schaible B., McClean S., Selfridge A. et al. Hypoxia modulates infection of epithelial cells by Pseudomonas aeruginosa. PLoS One. 2013;8(2): e56491. DOI: 10.1371/journal.pone.0056491.
49. Hams E., Saunders S.P., Cummins E.P. et al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. Shock. 2011;36(3):295–302. DOI: 10.1097/SHK.0b013e318225ad7e.
50. Serocki M., Bartoszewska S., Janaszak-Jasiecka A. et al. miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target. Angiogenesis. 2018;21(2):183–202. DOI: 10.1007/s10456-018-9600-2.
2. Colgan S.P., Campbell E.L., Kominsky D.J. Hypoxia and mucosal inflammation. Ann Rev Pathol. 2016;11:77–100. DOI: 10.1146/annurev-pathol-012615-044231.
3. Cummins E.P., Keogh C.E., Crean D., Taylor C.T. The role of HIF in immunity and inflammation. Mol Aspects Med. 2016;47–48:24–34. DOI: 10.1016/j.mam.2015.12.004.
4. Taylor C.T., Doherty G., Fallon P.G., Cummins E.P. Hypoxia-dependent regulation of inflammatory pathways in immune cells. J Clin Invest. 2016;126(10):3716–3724. DOI: 10.1172/JCI84433.
5. Taylor C.T., Colgan S.P. Regulation of immunity and inflammation by hypoxia in immunological niches. Nat Rev Immunol. 2017;17(12):774–785. DOI: 10.1038/nri.2017.103.
6. Biddlestone J., Bandarra D., Rocha S. The role of hypoxia in inflammatory disease (review). Int J Mol Med. 2015;35(4):859–869. DOI: 10.3892/ijmm.2015.2079.
7. Semenza G.L. Hypoxia-inducible factors in physiology and medicine. Cell. 2012;148(3):399–408. DOI: 10.1016/j.cell.2012.01.021.
8. Ratcliffe P.J. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. J Physiol. 2013;591(8):2027–2042. DOI: 10.1113/jphysiol.2013.251470.
9. Лукьянова Л.Д., Кирова Ю.И., Сукоян Г.В. Сигнальные механизмы адаптации к гипоксии и их роль в системной регуляции. Биологические мембраны. 2012;29(4):238–252. [Lukyanova L.D., Kirova Yu.I., Sukoyan G.V. Signaling mechanisms of adaptation to hypoxia and its role in systemic regulation. Biologicheskie membrany. 2012;29(4): 238–252 (in Russ.)].
10. Moniz S., Biddlestone J., Rocha S. Grow2: the HIF system, energy homeostasis and the cell cycle. Histol Histopathol. 2014;29(5):589–600. DOI: 10.14670/HH-29.10.589.
11. Zhang P., Yao Q., Lu L. et al. Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia. Cell Rep. 2014;6(6):1110–1121. DOI: 10.1016/j.celrep.2014.02.011.
12. Duan C. Hypoxia-inducible factor 3 biology: complexities and emerging themes. Am. J. Physiol. Cell Physiol. 2016;310(4): C260–269. DOI: 10.1152/ajpcell.00315.2015.
13. Kaelin W.G., Ratcliffe P.J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell. 2008;30(4):393–402. DOI: 10.1016/j.molcel.2008.04.009.
14. Krzywinska E., Stockmann C. Hypoxia, metabolism and immune cell function. Biomedicines. 2018;6(2):56. DOI: 10.3390/biomedicines6020056.
13. Dengler V.L., Galbraith M., Espinosa J.M. Transcriptional regulation by hypoxia inducible factors. Crit Rev. Biochem. Mol. Biol. 2014;49(1):1–15. DOI: 10.3109/10409238.2013.838205.
16. Lenihan C.R., Taylor C.T. The impact of hypoxia on cell death pathways. Biochem Soc Trans. 2013;41(2):657–663. DOI: 10.1042/BST20120345.
17. D’Ignazio L., Bandarra D., Rocha S. NF-κB and HIF crosstalk in immune responses. FEBS J. 2016;283(3):413–424. DOI: 10.1111/febs.13578.
18. Hoenderdos K., Lodge K.M., Hirs R.A. et al. Hypoxia upregulates neutrophil degranulation and potential for tissue injury. Thorax. 2016;71(11):1030–1038. DOI: 10.1136/thoraxjnl-2015-207604.
19. Polke M., Seiler F., Lepper P.M. et al. Hypoxia and the hypoxia-regulated transcription factor HIF-1α suppress the host defence of airway epithelial cells. Innate Immun. 2017;23(4):373–380. DOI: 10.1177/1753425917698032.
20. Ito Y., Ahmad A., Kewley E., Mason R.J. Hypoxia-inducible factor regulates expression of surfactant protein in alveolar type II cells in vitro. Am J Respir Cell Mol Biol. 2011;45(5):938–945. DOI: 10.1165/rcmb.2011-0052OC.
21. Bandarra D., Biddlestone J., Mudie S. et al. HIF-1 alpha restricts NF-kappaB-dependent gene expression to control innate immunity signals. Dis Model Mech. 2015;8(2):169–181. DOI: 10.1242/dmm.017285. 22. Scholz C.C., Taylor C.T. Hydroxylase-dependent regulation of the NF-κB pathway. Biol Chem. 2013;394(4):479–493. DOI: 10.1515/hsz-2012-0338.
23. Schuliga M. NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 2015;5(3):1266–1283. DOI: 10.3390/biom5031266.
24. Титова О.Н., Кузубова Н.А., Лебедева Е.С. и др. Противовоспалительный и регенеративный эффект подавления гипоксийного сигналинга на модели хронической обструктивной болезни легких. Пульмонология. 2018;28(2):169–176. [Titova O.N., Kuzubova O.N., Lebedeva E.S. et al. Anti-inflammatory and regenerative effects of hypoxic signaling inhibition in a model of COPD. Russian Pulmonology Journal. 2018;28(2):169–176 (in Russ.)]. DOI:10.18093/0869-0189-2018-28-2-169-176].
25. Tao J.H., Barbi J., Pan F. Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the theme: Cellular responses to hypoxia. Am J Physiol Cell Physiol. 2015;309(9):580–589. DOI: 10.1152/ajpcell.00204.2015.
26. Corcoran S.E., O’Neill L.A. HIF1α and metabolic reprogramming in inflammation. J Clin Invest. 2016;126(10):3699–3707. DOI: 10.1172/JCI84431.
27. Золотухин П.В., Беланова А.А., Празднова Е.В. и др. Митохондрии как сигнальный узел и мишень для отключения феноптоза. Биохимия. 2016;81(4):465–475. [Zolotuhin P.V., Belanova A.A., Prazdnova E.V. et al. Mitochondria as a signaling hub and target for phenoptosis shutdown, Biochemistry (Moscow). 2016;81(4):465–475 (in Russ.)].
28. Briston T., Stephen J.M., Thomas L.W. et al. VHL-mediated regulation of CHCHD4 and mitochondrial function. Front Oncol. 2018;8:388. DOI: 10.3389/fonc.2018.00388.
29. O’Neill L.A., Kishton R.J., Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16(9):553–565. DOI: 10.1038/nri.2016.70.
30. Halligan D.N., Murphy S.J., Taylor C.T. The hypoxia-inducible factor (HIF) couples immunity with metabolism. Semin Immunol. 2016;28(5):469–477. DOI: 10.1016/j.smim.2016.09.004.
31. Harris A.J., Thompson A.R., Whyte M.K., Walmsley S.R. HIF-mediated innate immune responses: cell signaling and therapeutic implications. Hypoxia (Auckl). 2014;2:47–58. DOI: 10.2147/HP.S50269.
32. Lin N., Simon M.C. Hypoxia-inducible factors: key regulators of myeloid cells during inflammation. J Clin Invest. 2016;126(10):3661–3671. DOI: 10.1172/JCI84426.
33. Hammami A., Charpentier T., Smans M., Stäger S. IRF-5-mediated inflammation limits CD8+ T Cell expansion by inducing HIF-1α and impairing dendritic cell functions during Leishmania infection. PLoS Pathog. 2015;11(6): e1004938. DOI: 10.1371/journal.ppat.1004938.
34. Mascanfroni I.D., Takenaka M.C., Yeste A. et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α Nat. Med. 2015;21(6):638–646. DOI: 10.1038/nm.3868.
35. Tyrakis P.A., Palazon A., Macias D. et al. S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate. Nature. 2016;540(7632):236–241. DOI: 10.1038/nature20165.
36. Phan A.T., Doedens A.L., Palazon A. et al. Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection. Immunity. 2016;45(5):1024–1037. DOI: 10.1016/j.immuni.2016.10.017.
37. Palazon A., Tyrakis P.A., Macias D. et al. An HIF-1α/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell. 2017;32(5):669–683.e5. DOI: 10.1016/j.ccell.2017.10.003.
38. Cho S.H., Raybuck A.L., Stengel K. et al. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system. Nature. 2016;537(7619):234–238. DOI: 10.1038/nature19334.
39. Crotty Alexander L.E., Akong-Moore K., Feldstein S. et al. Myeloid cell HIF-1α regulates asthma airway resistance and eosinophil function. J Mol Med. 2013;91(5):637–644. DOI: 10.1007/s00109-012-0986-9.
40. Loftus R.M., Finlay D.K. Immunometabolism: Cellular metabolism turns immune regulator. J Biol Chem. 2016;291(1):1–10. DOI: 10.1074/jbc.R115.693903.
41. Branitzki-Heinemann K., Möllerherm H., Völlger L. et al. Formation of neutrophil extracellular traps under low oxygen level. Front. Immunol. 2016;7:518. DOI: 10.3389/fimmu.2016.00518.
42. Möllerherm H., von Köckritz-Blickwede M., Branitzki-Heinemann K. Antimicrobial activity of mast cells: Role and relevance of extracellular DNA traps. Front. Immunol. 2016;7:265. DOI: 10.3389/fimmu.2016.00265.
43. Diebold L., Chandel N.S. Mitochondrial ROS regulation of proliferating cells. Free Radic Biol Med. 2016;100:86–93. DOI: 10.1016/j.freeradbiomed.2016.04.198.
44. Thomas L.W., Ashcroft M. Exploring the molecular interface between hypoxia-inducible factor signalling and mitochondria. Cell Mol. Life Sci. 2019;76(9):1759–1777. DOI: 10.1007/s00018-019-03039-y.
45. Singh C.K., Chhabra G., Ndiaye M.A. et al. The role of sirtuins in antioxidant and redox signaling. Antioxid. Redox Signal. 2018;28(8):643–661. DOI: 10.1089/ars.2017.7290.
46. Ivan M., Kaelin W.G., Jr. The EGLN-HIF O2-sensing system: multiple inputs and feedbacks. Mol Cell. 2017;66(6):772–779. DOI: 10.1016/j.molcel.2017.06.002.
47. Fasano C., Disciglio V., Bertora S. et al. FOXO3a from the nucleus to the mitochondria: A round trip in cellular stress response. Cells. 2019;8(9): pii: E1110. DOI: 10.3390/cells8091110.
48. Schaible B., McClean S., Selfridge A. et al. Hypoxia modulates infection of epithelial cells by Pseudomonas aeruginosa. PLoS One. 2013;8(2): e56491. DOI: 10.1371/journal.pone.0056491.
49. Hams E., Saunders S.P., Cummins E.P. et al. The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10 production by B1 cells. Shock. 2011;36(3):295–302. DOI: 10.1097/SHK.0b013e318225ad7e.
50. Serocki M., Bartoszewska S., Janaszak-Jasiecka A. et al. miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target. Angiogenesis. 2018;21(2):183–202. DOI: 10.1007/s10456-018-9600-2.
This work is licensed under a Creative Commons «Attribution» 4.0 License.
Previous article
Next article
Распечатать