Hipoksi-İndüklenebilir Faktör-1 Alfa’nın Doğası ve İnsan Biyolojisindeki Rolü

Yıl 2024, Cilt: 5 Sayı: 2, 48 - 55, 30.04.2024

Nurettin Onur Kutlu İlhan Yaylım

Öz

Hypoxia-Inducible Factor-1 alpha, oksijen seviyelerine karşı hücresel yanıtta merkezi bir rol oynayan kritik bir transkripsiyon faktörüdür. HIF-1α, ökaryotlar ve tüm omurgalı/
omurgasız canlıların tümünde oksijensiz ortamda hücresel
düzeyde adaptasyon sağlanmasında görevlidir. On beş kromozomda yüzden fazla gene bağlanma noktaları olduğu belirlenmiştir. Metabolizma, anjiyogenez, hematopoez, epitel
hücrelerinin çoğalması ve göçü, eritropoez, bağışıklık, inflamasyon, kanser, epigenetik düzenlenme, apoptosis ve otofajide kritik bir rol oynar. Bu derlemede, HIF-1α'nın yapısı,
düzenlenmesi ile hipoksi, yangı, yaralanma, iskemi ve kanser
gibi patolojik süreçlerle olan etkileşimlerini son bilimsel gelişmeler ışığında sunmayı amaçlıyoruz.

Anahtar Kelimeler

HIF-1 alfa, hipoksi, anjiogenez, metabolizma, yangı, kanser, iskemi

Kaynakça

• 1. Ajdukovic, J., HIF-1--a big chapter in the cancer tale. Exp Oncol, 2016. 38(1): p. 9-12.
• 2. Kaelin, W.G., Jr. and P.J. Ratcliffe, Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell, 2008. 30(4): p. 393-402.
• 3. Majmundar, A.J., W.J. Wong, and M.C. Simon, Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell, 2010. 40(2): p. 294-309.
• 4. Semenza, G.L., Hypoxia-inducible factors in physiology and medicine. Cell, 2012. 148(3): p. 399-408.
• 5. Xia, X., et al., Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A, 2009. 106(11): p. 4260-5.
• 6. Weidemann, A. and R.S. Johnson, Biology of HIF-1alpha. Cell Death Differ, 2008. 15(4): p. 621-7.
• 7. Palazon, A., et al., HIF transcription factors, inflammation, and immunity. Immunity, 2014. 41(4): p. 518-28.
• 8. Keith, B., R.S. Johnson, and M.C. Simon, HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer, 2011. 12(1): p. 9-22.
• 9. Schodel, J., et al., High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood, 2011. 117(23): p. e207-17.
• 10. Semenza, G.L., Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol, 2014. 9: p. 47-71.
• 11. Toth, R.K. and N.A. Warfel, Strange Bedfellows: Nuclear Factor, Erythroid 2-Like 2 (Nrf2) and Hypoxia-Inducible Factor 1 (HIF-1) in Tumor Hypoxia. Antioxidants (Basel), 2017. 6(2).
• 12. Yang, C., et al., HIF-1: structure, biology and natural modulators. Chin J Nat Med, 2021. 19(7): p. 521-527.
• 13. Albadari, N., S. Deng, and W. Li, The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy. Expert Opin Drug Discov, 2019. 14(7): p. 667-682.
• 14. Duan, C., Hypoxia-inducible factor 3 biology: complexities and emerging themes. Am J Physiol Cell Physiol, 2016. 310(4): p. C260-9.
• 15. Kewley, R.J., M.L. Whitelaw, and A. Chapman-Smith, The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol, 2004. 36(2): p. 189-204.
• 16. Chowdhury, R., et al., Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Nat Commun, 2016. 7: p. 12673.
• 17. Bakker, W.J., et al., Differential regulation of Foxo3a target genes in erythropoiesis. Mol Cell Biol, 2007. 27(10): p. 3839-3854.
• 18. Carbia-Nagashima, A., et al., RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell, 2007. 131(2): p. 309-23.
• 19. Cheng J, K.X., Zhang S, Yeh ET., SUMO-specific protease 1 is essential for stabilization of HIF1alpha during hypoxia. Cell, 2007. 3(131): p. 584-595.
• 20. Luo, W., et al., Hsp70 and CHIP selectively mediate ubiquitination and degradation of hypoxia-inducible factor (HIF)-1alpha but Not HIF-2alpha. J Biol Chem, 2010. 285(6): p. 3651-3663.
• 21. Shatrov, V.A., et al., Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation via redox-dependent mechanisms. Blood, 2003. 101(12): p. 4847-9.
• 22. Simon, M.C., Siah proteins, HIF prolyl hydroxylases, and the physiological response to hypoxia. Cell, 2004. 117(7): p. 851-3.
• 23. Isaacs, J.S., et al., Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha-degradative pathway. J Biol Chem, 2002. 277(33): p. 29936-44.
• 24. van de Sluis, B., et al., COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70. PLoS One, 2009. 4(10): p. e7332.
• 25. Qutub, A.A. and A.S. Popel, Reactive oxygen species regulate hypoxia-inducible factor 1alpha differentially in cancer and ischemia. Mol Cell Biol, 2008. 28(16): p. 5106-19.
• 26. Chen, C., et al., Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem, 2001. 276(12): p. 9519-25.
• 27. Liu, M., et al., Novel Therapeutic Targets for Hypoxia-Related Cardiovascular Diseases: The Role of HIF-1. Front Physiol, 2020. 11: p. 774.
• 28. Lee, K., et al., Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci U S A, 2009. 106(42): p. 17910-5.
• 29. Semenza, G.L., Regulation of cancer cell metabolism by hypoxia-inducible factor 1. Semin Cancer Biol, 2009. 19(1): p. 12-6.
• 30. Semenza, G.L., HIF-1 inhibitors for cancer therapy: from gene expression to drug discovery. Curr Pharm Des, 2009. 15(33): p. 3839-43.
• 31. Harada, H., et al., The Akt/mTOR pathway assures the synthesis of HIF-1alpha protein in a glucose- and reoxygenation-dependent manner in irradiated tumors. J Biol Chem, 2009. 284(8): p. 5332-42.
• 32. Kaelin, W.G., Proline hydroxylation and gene expression. Annu Rev Biochem, 2005. 74: p. 115-28.
• 33. Zheng, J., et al., HIF-1alpha in myocardial ischemia-reperfusion injury (Review). Mol Med Rep, 2021. 23(5).
• 34. Chang, H., et al., Effect of sedation with dexmedetomidine or propofol on gastrointestinal motility in lipopolysaccharide-induced endotoxemic mice. BMC Anesthesiol, 2020. 20(1): p. 227.
• 35. Dehne, N. and B. Brune, HIF-1 in the inflammatory microenvironment. Exp Cell Res, 2009. 315(11): p. 1791-7.
• 36. Ke, Q. and M. Costa, Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol, 2006. 70(5): p. 1469-80.
• 37. Kim, J.W., et al., HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab, 2006. 3(3): p. 177-85.
• 38. Lu, H., R.A. Forbes, and A. Verma, Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem, 2002. 277(26): p. 23111-5.
• 39. Masoud, G.N. and W. Li, HIF-1alpha pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B, 2015. 5(5): p. 378-89.
• 40. Semenza, G.L., HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest, 2013. 123(9): p. 3664-71.
• 41. Papandreou, I., et al., HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab, 2006. 3(3): p. 187-97.
• 42. Fukuda, R., et al., HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell, 2007. 129(1): p. 111-22.
• 43. Semenza, G.L., Oxygen sensing, homeostasis, and disease. N Engl J Med, 2011. 365(6): p. 537-47.
• 44. Vander Heiden, M.G., L.C. Cantley, and C.B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 2009. 324(5930): p. 1029-33.
• 45. Marchetti, M., COVID-19-driven endothelial damage: complement, HIF1, and ABL2 are potential pathways of damage and targets for cure. Ann Hematol, 2020. 99(8): p. 1701-1707.
• 46. Devraj, G., et al., Hypoxia and HIF-1 activation in bacterial infections. Microbes Infect, 2017. 19(3): p. 144-156.
• 47. Frede, S., U. Berchner-Pfannschmidt, and J. Fandrey, Regulation of hypoxia-inducible factors during inflammation. Methods Enzymol, 2007. 435: p. 405-19.
• 48. Blouin, C.C., et al., Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1alpha. Blood, 2004. 103(3): p. 1124-30.
• 49. Peyssonnaux, C., et al., HIF-1alpha expression regulates the bactericidal capacity of phagocytes. J Clin Invest, 2005. 115(7): p. 1806-15.
• 50. Rius, J., et al., NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature, 2008. 453(7196): p. 807-11.
• 51. Rankin, E.B., et al., Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Invest, 2007. 117(4): p. 1068-77.
• 52. Semenza, G.L., Regulation of physiological responses to continuous and intermittent hypoxia by hypoxia-inducible factor 1. Exp Physiol, 2006. 91(5): p. 803-6.
• 53. Rosenberger, C., et al., Expression of hypoxia-inducible factor-1alpha and -2alpha in hypoxic and ischemic rat kidneys. J Am Soc Nephrol, 2002. 13(7): p. 1721-32.
• 54. Haase, V.H., Hypoxic regulation of erythropoiesis and iron metabolism. Am J Physiol Renal Physiol, 2010. 299(1): p. F1-13.
• 55. Greijer, A.E. and E. van der Wall, The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol, 2004. 57(10): p. 1009- 14.
• 56. Sermeus, A. and C. Michiels, Reciprocal influence of the p53 and the hypoxic pathways. Cell Death Dis, 2011. 2(5): p. e164.
• 57. Bellot, G., et al., Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol, 2009. 29(10): p. 2570-81.
• 58. Mazure, N.M. and J. Pouyssegur, Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol, 2010. 22(2): p. 177-80.
• 59. Yamashita, T., et al., Impairment of HIF-2alpha Expression Induced the Compensatory Overexpression of the HIF-1alpha/SDF-1 Axis to Promote Wound Healing. Stem Cells Dev, 2023. 32(19-20): p. 592-605.
• 60. Xu, W., et al., Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1alpha signalling. J Cell Mol Med, 2019. 23(3): p. 1899- 1907.
• 61. Botusan, I.R., et al., Stabilization of HIF-1alpha is critical to improve wound healing in diabetic mice. Proc Natl Acad Sci U S A, 2008. 105(49): p. 19426-31.
• 62. Dong, P., Q. Li, and H. Han, HIF-1alpha in cerebral ischemia (Review). Mol Med Rep, 2022. 25(2).
• 63. Zhang, Z., et al., PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review). Mol Med Rep, 2018. 18(4): p. 3547-3554.
• 64. Ma, Z., et al., PDK4 facilitates fibroblast functions and diabetic wound healing through regulation of HIF-1alpha protein stability and gene expression. FASEB J, 2023. 37(10): p. e23215.
• 65. Jia, Z., et al., Ischemic Postconditioning Protects Against Intestinal Ischemia/Reperfusion Injury via the HIF-1alpha/miR-21 Axis. Sci Rep, 2017. 7(1): p. 16190.
• 66. Semenza, G.L., Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 2003. 3(10): p. 721-32.
• 67. Liao, D. and R.S. Johnson, Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev, 2007. 26(2): p. 281-90.
• 68. Lu, X. and Y. Kang, Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clin Cancer Res, 2010. 16(24): p. 5928-35.
• 69. Palazon, A., et al., Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res, 2012. 18(5): p. 1207-13.
• 70. Shen, X., et al., Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Res, 2009. 27(10): p. 1298-305.
• 71. Gilkes, D.M. and G.L. Semenza, Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol, 2013. 9(11): p. 1623-36.