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Regulation of Hypoxia-Inducible Factor-1a by Reactive Oxygen Species : New Developments in an Old Debate
Abstract
Hypoxia-Inducible Factor-1 (HIF-1) has been largely studied for its role in cell survival in hypoxic conditions. The regulation of HIF-1 is a complex process and involves a number of molecules and pathways. Among these mechanisms a direct regulatory role of reactive oxygen species (ROS) on HIF-1 alpha subunit has received a great deal of attention and the existing body of literature includes many contradictory findings. Other intermediates such as nitric oxide (NO), specific microRNAs (miR), and transcriptional and post-translational modification have also been implicated as players in ROS mediated HIF-1a regulation. The focus of this review is to present the past conflicting evidence along with more recent findings in order to relate various aspects of this complex process. Aside from the direct role of ROS on HIF-1a regulation under hypoxia and normoxia, we analyzed the effect of different sources and concentrations of NO and the interplay between superoxide (SO) and NO in this process. We also present findings on transcriptional and translational regulation of HIF-1a via ROS and the interplay with microRNAs in this process. This review further provides insight on ERK and PI3K/AKT signaling as a common mechanism relating several pathways of ROS mediated HIF-1a regulation. Ultimately further research and discovery regarding HIF-1 regulation by oxidative stress is warranted for better understanding of disease development and potential therapeutics for pathologies such as canc…
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“Therefore, it is plausible that increased levels of 2-HG may enable a switch to an entirely HIF-independent mechanism.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [160]
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1 retracted
Kasuno, K., Takabuchi, S., Fukuda, K., Kizaka‐Kondoh, S., Yodoi, J., Adachi, T., Semenza, G. L., & Hirota, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308197200 · Cited by 226
RetractedJaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735
Chandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., & Schumacker, P. T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001914200 · Cited by 2,000
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545
Hydroxylation of HIF-1: Oxygen Sensing at the Molecular Level
Semenza, G. L. (2004) · Physiology · doi:10.1152/physiol.00001.2004 · Cited by 923
Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
Brunelle, J. K., Bell, E. L., Quesada, N. M., Vercauteren, K., Tiranti, V., Zeviani, M., Scarpulla, R. C., & Chandel, N. S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.002 · Cited by 763
Hypoxia-Inducible mir-210 Regulates Normoxic Gene Expression Involved in Tumor Initiation
Huang, X., Ding, L., Bennewith, K. L., Tong, R. T., Welford, S. M., Ang, K. K., Story, M. D., Le, Q., & Giaccia, A. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.006 · Cited by 634
Lenaz, G. (2001) · IUBMB Life · doi:10.1080/15216540152845957 · Cited by 585
Bell, E. L., Klimova, T. A., Eisenbart, J., Moraes, C. T., Murphy, M. P., Budinger, G. R. S., & Chandel, N. S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200609074 · Cited by 568
MiR-21 Induced Angiogenesis through AKT and ERK Activation and HIF-1α Expression
Liu, L.-Z., Li, C.-Y., Chen, Q., Yi, J., Carpenter, R. L., Jiang, Y., Kung, H., Lai, L., & Jiang, B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019139 · Cited by 509
Kimura, H., Weisz, A., Kurashima, Y., Hashimoto, K., Ogura, T., D’Acquisto, F., Addeo, R., Makuuchi, M., & Esumi, H. (2000) · Blood · doi:10.1182/blood.v95.1.189 · Cited by 437
Puisségur, M.-P., Mazure, N. M., Bertero, T., Pradelli, L. A., Grosso, S., Robbe-Sermesant, K., Maurin, T., Lebrigand, K., Cardinaud, B., Hofman, V., et al. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.119 · Cited by 430
Nitric Oxide Impairs Normoxic Degradation of HIF-1α by Inhibition of Prolyl Hydroxylases
Metzen, E., Zhou, J., Jelkmann, W., Fandrey, J., & Brüne, B. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-12-0791 · Cited by 414
MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300
Sang, N., Stiehl, D. P., Bohensky, J., Leshchinsky, I., Srinivas, V., & Caro, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209702200 · Cited by 370
Oxygen Sensing, Hypoxia-Inducible Factor-1 and the Regulation of Mammalian Gene Expression
Ratcliffe, P. J., O’rourke, J. F., Maxwell, P. H., & Pugh, C. W. (1998) · Journal of Experimental Biology · doi:10.1242/jeb.201.8.1153 · Cited by 368
Inhibition of Hypoxia-inducible Factor 1 Activation by Carbon Monoxide and Nitric Oxide
Huang, E. L., Willmore, W. G., Gu, J., Goldberg, M. A., & Bunn, H. F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.13.9038 · Cited by 288
Accumulation of HIF-1α under the influence of nitric oxide
Sandau, K. B., Fandrey, J., & Brüne, B. (2001) · Blood · doi:10.1182/blood.v97.4.1009 · Cited by 263
Mateo, J., García‐Lecea, M., Cadenas, S., HERNÁNDEZ, C., & Moncada, S. (2003) · Biochemical Journal · doi:10.1042/bj20031155 · Cited by 256
Antioxidant/Pro-oxidant Equilibrium Regulates HIF-1α and NF-κB Redox Sensitivity
Haddad, J. J., Olver, R. E., & Land, S. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000737200 · Cited by 239
Lin, Y., Liu, X., Cheng, Y., Yang, J., Huo, Y., & Zhang, C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m806920200 · Cited by 230
Palmer, L. A., Gaston, B. M., & Johns, R. A. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.6.1197 · Cited by 191
Chua, Y. L., Dufour, E., Dassa, E. P., Rustin, P., Jacobs, H. T., Taylor, C. T., & Hagen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.158485 · Cited by 189
MicroRNA-21 Modulates the Levels of Reactive Oxygen Species by Targeting SOD3 and TNF α
Zhang, X., Ng, W. L., Wang, P., Tian, L., Werner, E., Wang, H., Doetsch, P. W., & Wang, Y. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0639 · Cited by 181
Mutharasan, R. K., Nagpal, V., Ichikawa, Y., & Ardehali, H. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01080.2010 · Cited by 175
Effect of Altered Redox States on Expression and DNA-Binding Activity of Hypoxia-Inducible Factor 1
Wang, G. L., Jiang, B., & Semenza, G. L. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2005 · Cited by 173
Yasinska, I. M., & Sumbayev, V. V. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00807-x · Cited by 156
Kim, J. H., Park, S., Song, S.-Y., Kim, J. K., & Sung, J.-H. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.117 · Cited by 154
Oxygen-Dependent and -Independent Regulation of HIF-1alpha
Chun, Y. S., Kim, M., & Park, J. W. (2002) · Journal of Korean Medical Science · doi:10.3346/jkms.2002.17.5.581 · Cited by 152
The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity
Masson, N., Singleton, R. S., Sekirnik, R., Trudgian, D. C., Ambrose, L. J. A., Miranda, M. X., Tian, Y., Kessler, B. M., Schofield, C. J., & Ratcliffe, P. J. (2012) · EMBO Reports · doi:10.1038/embor.2012.9 · Cited by 148
Redox regulation of pro-inflammatory cytokines and IκB-α/NF-κB nuclear translocation and activation
Haddad, J. J. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00947-6 · Cited by 148
Koshikawa, N., Hayashi, J.-I., Nakagawara, A., & Takenaga, K. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.054221 · Cited by 147
Induction of Hypoxia-Inducible-Factor 1 by Nitric Oxide Is Mediated via the PI 3K Pathway
Sandau, K. B., Faus, H., & Brüne, B. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3789 · Cited by 130
Nitric oxide and superoxide: Interference with hypoxic signaling
Brüne, B., & ZHOU, J. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.03.005 · Cited by 126
Superoxide fluxes limit nitric oxide-induced signaling
Thomas, D. D., Ridnour, L. A., Espey, M. G., Donzelli, S., Ambs, S., Hussain, S. P., Harris, C. C., DeGraff, W., Roberts, D. D., Mitchell, J. B., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602242200 · Cited by 121
HIF‐1α protein as a target for S‐nitrosation
Sumbayev, V. V., Budde, A., Zhou, J., & Brüne, B. (2003) · FEBS Letters · doi:10.1016/s0014-5793(02)03887-5 · Cited by 108
Hielscher, A. C., & Gerecht, S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.09.015 · Cited by 108
Du, J., Xu, R., Hu, Z., Tian, Y., Zhu, Y., Gu, L., & Zhou, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025213 · Cited by 106
The cellular response to hypoxia: tuning the system with microRNAs
Loscalzo, J. (2010) · Journal of Clinical Investigation · doi:10.1172/jci45105 · Cited by 105
Manganese Superoxide Dismutase Modulates Hypoxia-Inducible Factor-1α Induction via Superoxide
Kaewpila, S., Venkataraman, S., Buettner, G. R., & Oberley, L. W. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2635 · Cited by 103
Oxygen versus Reactive Oxygen in the Regulation of HIF-1α: The Balance Tips
Hagen, T. (2012) · Biochemistry Research International · doi:10.1155/2012/436981 · Cited by 100
Regulation of Cytokine‐Induced HIF‐1α Expression in Rheumatoid Synovial Fibroblasts
Westra, J., Brouwer, E., Bos, R., Posthumus, M. D., der Meer, B. D., Kallenberg, C. G. M., & Limburg, P. C. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1422.035 · Cited by 94
Haddad, J. J. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00870-x · Cited by 79
Reactive oxygen species attenuate nitric-oxide-mediated hypoxia-inducible factor-1α stabilization
Köhl, R., Zhou, J., & Brüne, B. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.12.012 · Cited by 69
Owens, K. M., Aykin‐Burns, N., Dayal, D., Coleman, M. C., Domann, F. E., & Spitz, D. R. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.435 · Cited by 52
Evaluation of hypoxia inducible factor expression in inflammatory and neurodegenerative brain models
de Lemos, M. L., de la Torre, A. V., Petrov, D., Brox, S., Folch, J., Pallàs, M., Lazarowski, A., Beas‐Zárate, C., Auladell, C., & Camins, A. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.04.011 · Cited by 47
Sasabe, E., Yang, Z., Ohno, S., & Yamamoto, T. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.02.013 · Cited by 45
Xue, Y., Li, N., Yang, J., Chen, Y., Yang, L.-L., & Liu, W. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00970.2010 · Cited by 22
Weitnauer, M., Petry, A., BelAiba, R. S., & Görlach, A. (2012) · Thrombosis and Haemostasis · doi:10.1160/th12-04-0277 · Cited by 12
Research works printed but not linked: 2
- Brüne, 2007, Methods in enzymology, 463
- Hagen, 2012, Oxygen versus Reactive Oxygen in the Regulation of HIF-1: The Balance Tips, Biochem Res Int, e436981
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“…of HIF is complex, and a variety ofmechanisms have been implicated in its stabilization, includingmicroRNA, other post-translationalmodifications, and intracellular signaling cascades (e.g., ERK and AKT), in addition to ROS and PHD inhibition (Movafagh et al., 2015; Yee Koh et al., 2008).”
Metadata
- Authors
- Movafagh, S., Crook, S., & Vo, K.
- Affiliations
- Shenandoah University (US)
- Corresponding author
- Movafagh, Shahrzad
- ORCID
- Movafagh, Shahrzad
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2015-03-09
- Volume
- 116
- Issue
- 5
- Pages
- 696-703
- ISSN
- 0730-2312 (ISSN-L)
- OpenAlex
- W1899746275
- Cited by
- 469
- References
- 50
- Citations by year
- 2026: 23 · 2025: 42 · 2024: 39 · 2023: 56 · 2022: 56 · 2021: 66 · 2020: 54 · 2019: 39 · 2018: 29 · 2017: 31 · 2016: 22 · 2015: 12
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- hypoxia-inducible factor-1α, reactive oxygen species, nitric oxide, superoxide, microRNA, post-translational modification, transcriptional regulation, ERK signaling, PI3K/Akt signaling, oxidative stress, hypoxia, ischemia-reperfusion injury, cancer
- MeSH terms
- Humans, Mitochondria, Nitric Oxide, Superoxides, Signal Transduction, Cell Hypoxia, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, MicroRNAs, Proto-Oncogene Proteins c-akt, Hypoxia-Inducible Factor 1, alpha Subunit
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