123
Views
128
CrossRef citations to date
0
Altmetric
Article

Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1α Differentially in Cancer and Ischemia

&
Pages 5106-5119 | Received 11 Jan 2008, Accepted 30 May 2008, Published online: 27 Mar 2023

REFERENCES

  • Agani, F. H., P. Pichiule, J. C. Chavez, and J. C. LaManna. 2000. The role of mitochondria in the regulation of hypoxia-inducible factor 1 expression during hypoxia. J. Biol. Chem. 275:35863–35867.
  • Al-Ayash, A. I., and M. T. Wilson. 1979. The mechanism of reduction of single-site redox proteins by ascorbic acid. Biochem. J. 177:641–648.
  • Alon, U. 2007. An introduction to systems biology. Chapman & Hall, Boca Raton, FL.
  • Antunes, F., and E. Cadenas. 2001. Cellular titration of apoptosis with steady state concentrations of H2O2: submicromolar levels of H2O2 induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free Radic. Biol. Med. 30:1008–1018.
  • Antunes, F., and E. Cadenas. 2000. Estimation of H2O2 gradients across biomembranes. FEBS Lett. 475:121–126.
  • Arnold, R. S., J. Shi, E. Murad, A. M. Whalen, C. Q. Sun, R. Polavarapu, S. Parthasarathy, J. A. Petros, and J. D. Lambeth. 2001. Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1. Proc. Natl. Acad. Sci. USA 98:5550–5555.
  • Avshalumov, M. V., L. Bao, C. P. J., and M. E. Rice. 2007. H2O2 signaling in the nigrostriatal dopamine pathway via ATP-sensitive potassium channels: issues and answers. Antioxid. Redox Signal. 9:219–231.
  • Bell, E. L., and N. S. Chandel. 2007. Mitochondrial oxygen sensing: regulation of hypoxia-inducible factor by mitochondrial generated reactive oxygen species. Essays Biochem. 43:17–27.
  • Bell, E. L., T. A. Klimova, J. Eisenbart, C. T. Moraes, M. P. Murphy, G. R. Budinger, and N. S. Chandel. 2007. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J. Cell Biol. 177:1029–1036.
  • Bell, E. L., T. A. Klimova, J. Eisenbart, P. T. Schumacker, and N. S. Chandel. 2007. Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia. Mol. Cell. Biol. 27:5737–5745.
  • Bellisola, G., M. Casaril, G. B. Gabrielli, M. Caraffi, and R. Corrocher. 1987. Catalase activity in human hepatocellular carcinoma (HCC). Clin. Biochem. 20:415–417.
  • Beltran, F. J., M. Gonzalez, F. J. Rivas, and P. Alvarez. 1998. Fenton reagent advanced oxidation of polynuclear aromatic hydrocarbons in water. Water Air Soil Pollut. 105:685–700.
  • Bergeron, M., A. Y. Yu, K. E. Solway, G. L. Semenza, and F. R. Sharp. 1999. Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain. Eur. J. Neurosci. 11:4159–4170.
  • Bernaudin, M., A. S. Nedelec, D. Divoux, E. T. MacKenzie, E. Petit, and P. Schumann-Bard. 2002. Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain. J. Cereb. Blood Flow Metab. 22:393–403.
  • Bienert, G. P., A. L. Moller, K. A. Kristiansen, A. Schulz, I. M. Moller, J. K. Schjoerring, and T. P. Jahn. 2007. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J. Biol. Chem. 282:1183–1192.
  • Bienert, G. P., J. K. Schjoerring, and T. P. Jahn. 2006. Membrane transport of hydrogen peroxide. Biochim. Biophys. Acta 1758:994–1003.
  • Biswas, S., M. K. Gupta, D. Chattopadhyay, and C. K. Mukhopadhyay. 2007. Insulin-induced activation of hypoxia-inducible factor-1 requires generation of reactive oxygen species by NADPH oxidase. Am. J. Physiol. Heart Circ. Physiol. 292:H758–H566.
  • Boveris, A., N. Oshino, and B. Chance. 1972. The cellular production of hydrogen peroxide. Biochem. J. 128:617–630.
  • Bozzi, A., I. Mavelli, B. Mondovi, R. Strom, and G. Rotilio. 1981. Differential cytotoxicity of daunomycin in tumour cells is related to glutathione-dependent hydrogen peroxide metabolism. Biochem. J. 194:369–372.
  • Brunelle, J. K., E. L. Bell, N. M. Quesada, K. Vercauteren, V. Tiranti, M. Zeviani, R. C. Scarpulla, and N. S. Chandel. 2005. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell. Metab. 1:409–414.
  • Bychkov, R., K. Pieper, C. Ried, M. Milosheva, E. Bychkov, F. C. Luft, and H. Haller. 1999. Hydrogen peroxide, potassium currents, and membrane potential in human endothelial cells. Circulation 99:1719–1725.
  • Callapina, M., J. Zhou, T. Schmid, R. Kohl, and B. Brune. 2005. NO restores HIF-1α hydroxylation during hypoxia: role of reactive oxygen species. Free Radic. Biol. Med. 39:925–936.
  • Canbolat, O., J. Fandrey, and W. Jelkmann. 1998. Effects of modulators of the production and degradation of hydrogen peroxide on erythropoietin synthesis. Respir. Physiol. 114:175–183.
  • Cerutti, P. A. 1985. Prooxidant states and tumor promotion. Science 227:375–381.
  • Chance, B., H. Sies, and A. Boveris. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59:527–605.
  • Chandel, N. S., D. S. McClintock, C. E. Feliciano, T. M. Wood, J. A. Melendez, A. M. Rodriguez, and P. T. Schumacker. 2000. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J. Biol. Chem. 275:25130–25138.
  • Chang, T. C., C. J. Huang, K. Tam, S. F. Chen, K. T. Tan, M. S. Tsai, T. N. Lin, and S. K. Shyue. 2005. Stabilization of hypoxia-inducible factor-1α by prostacyclin under prolonged hypoxia via reducing reactive oxygen species level in endothelial cells. J. Biol. Chem. 280:36567–36574.
  • Chavez, J. C., F. Agani, P. Pichiule, and J. C. LaManna. 2000. Expression of hypoxia-inducible factor-1α in the brain of rats during chronic hypoxia. J. Appl. Physiol. 89:1937–1942.
  • Chavez, J. C., and J. C. LaManna. 2002. Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1. J. Neurosci. 22:8922–8931.
  • Chung-man Ho, J., S. Zheng, S. A. Comhair, C. Farver, and S. C. Erzurum. 2001. Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res. 61:8578–8585.
  • Deudero, J. J., C. Caramelo, M. C. Castellanos, F. Neria, R. Fernandez-Sanchez, O. Calabia, S. Penate, and F. R. Gonzalez-Pacheco. 2008. Induction of hypoxia-inducible factor 1alpha gene expression by vascular endothelial growth factor. Role of a superoxide-mediated mechanism. J. Biol. Chem. 283:11435–11444.
  • Dirnagl, U., U. Lindauer, A. Them, S. Schreiber, H. W. Pfister, U. Koedel, R. Reszka, D. Freyer, and A. Villringer. 1995. Global cerebral ischemia in the rat: online monitoring of oxygen free radical production using chemiluminescence in vivo. J. Cereb. Blood Flow Metab. 15:929–940.
  • Fandrey, J., S. Frede, and W. Jelkmann. 1994. Role of hydrogen peroxide in hypoxia-induced erythropoietin production. Biochem. J. 303:507–510.
  • Gerald, D., E. Berra, Y. M. Frapart, D. A. Chan, A. J. Giaccia, D. Mansuy, J. Pouyssegur, M. Yaniv, and F. Mechta-Grigoriou. 2004. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 118:781–794.
  • Ginouves, A., K. Ilc, N. Macias, J. Pouyssegur, and E. Berra. 2008. PHDs overactivation during chronic hypoxia “desensitizes” HIFα and protects cells from necrosis. Proc. Natl. Acad. Sci. USA 105:4745–4750.
  • Giorgio, M., M. Trinei, E. Migliaccio, and P. G. Pelicci. 2007. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat. Rev. Mol. Cell Biol. 8:722–728.
  • Gonzalez-Flecha, B., and B. Demple. 1997. Homeostatic regulation of intracellular hydrogen peroxide concentration in aerobically growing Escherichia coli. J. Bacteriol. 179:382–388.
  • Gottlieb, E., and I. P. Tomlinson. 2005. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat. Rev. Cancer 5:857–866.
  • Grisham, M. B., L. A. Hernandez, and D. N. Granger. 1986. Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am. J. Physiol. 251:G567–G574.
  • Guzy, R. D., B. Hoyos, E. Robin, H. Chen, L. Liu, K. D. Mansfield, M. C. Simon, U. Hammerling, and P. T. Schumacker. 2005. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell. Metab. 1:401–408.
  • Guzy, R. D., and P. T. Schumacker. 2006. Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp. Physiol. 91:807–819.
  • Guzy, R. D., B. Sharma, E. Bell, N. S. Chandel, and P. T. Schumacker. 2008. Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol. Cell. Biol. 28:718–731.
  • Haddad, J. J., and S. C. Land. 2001. A non-hypoxic, ROS-sensitive pathway mediates TNF-alpha-dependent regulation of HIF-1α. FEBS Lett. 505:269–274.
  • Hagen, T., C. T. Taylor, F. Lam, and S. Moncada. 2003. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1α. Science 302:1975–1978.
  • Hederstedt, L. 2003. Structural biology. Complex II is complex too. Science 299:671–672.
  • Herr, B., J. Zhou, S. Drose, and B. Brune. 2007. The interaction of superoxide with nitric oxide destabilizes hypoxia-inducible factor-1α. Cell Mol. Life Sci. 64:3295–3305.
  • Holmquist, L., G. Stuchbury, M. Steele, and G. Munch. 2007. Hydrogen peroxide is a true first messenger. J. Neural Transm. Suppl. 2007:39–41.
  • Ishii, N., M. Fujii, P. S. Hartman, M. Tsuda, K. Yasuda, N. Senoo- Matsuda, S. Yanase, D. Ayusawa, and K. Suzuki. 1998. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394:694–697.
  • Ishii, T., K. Yasuda, A. Akatsuka, O. Hino, P. S. Hartman, and N. Ishii. 2005. A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis. Cancer Res. 65:203–209.
  • Jensen, R. L. 2006. Hypoxia in the tumorigenesis of gliomas and as a potential target for therapeutic measures. Neurosurg. Focus 20:E24.
  • Jiang, Y., J. Wu, R. F. Keep, Y. Hua, J. T. Hoff, and G. Xi. 2002. Hypoxia-inducible factor-1α accumulation in the brain after experimental intracerebral hemorrhage. J. Cereb. Blood Flow Metab. 22:689–696.
  • Jung, S. N., W. K. Yang, J. Kim, H. S. Kim, E. J. Kim, H. Yun, H. Park, S. S. Kim, W. Choe, I. Kang, and J. Ha. 2008. Reactive oxygen species stabilize hypoxia inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells. Carcinogenesis 29:713–721.
  • King, A., M. A. Selak, and E. Gottlieb. 2006. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25:4675–4682.
  • Kohl, R., J. Zhou, and B. Brune. 2006. Reactive oxygen species attenuate nitric-oxide-mediated hypoxia-inducible factor-1α stabilization. Free Radic. Biol. Med. 40:1430–1442.
  • Koivunen, P., M. Hirsila, A. M. Remes, I. E. Hassinen, K. I. Kivirikko, and J. Myllyharju. 2007. Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle intermediates: possible links between cell metabolism and stabilization of HIF. J. Biol. Chem. 282:4524–4532.
  • Kozhukhar, A. V., I. M. Yasinska, and V. V. Sumbayev. 2006. Nitric oxide inhibits HIF-1α protein accumulation under hypoxic conditions: implication of 2-oxoglutarate and iron. Biochimie 88:411–418.
  • Kwon, S. J., J. J. Song, and Y. J. Lee. 2005. Signal pathway of hypoxia-inducible factor-1α phosphorylation and its interaction with von Hippel-Lindau tumor suppressor protein during ischemia in MiaPaCa-2 pancreatic cancer cells. Clin. Cancer Res. 11:7607–7613.
  • Lacy, F., M. T. Kailasam, D. T. O'Connor, G. W. Schmid-Schonbein, and R. J. Parmer. 2000. Plasma hydrogen peroxide production in human essential hypertension: role of heredity, gender, and ethnicity. Hypertension 36:878–884.
  • Laurent, A., C. Nicco, C. Chereau, C. Goulvestre, J. Alexandre, A. Alves, E. Levy, F. Goldwasser, Y. Panis, O. Soubrane, B. Weill, and F. Batteux. 2005. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 65:948–956.
  • Leonardi, F., L. Attorri, R. D. Benedetto, A. D. Biase, M. Sanchez, F. P. Tregno, M. Nardini, and S. Salvati. 2007. Docosahexaenoic acid supplementation induces dose and time dependent oxidative changes in C6 glioma cells. Free Radic. Res. 41:748–756.
  • Lopez-Lazaro, M. 2007. Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy. Cancer Lett. 252:1–8.
  • Lovstad, R. A. 2003. A kinetic study on iron stimulation of the xanthine oxidase dependent oxidation of ascorbate. Biometals 16:435–439.
  • Lu, H., C. L. Dalgard, A. Mohyeldin, T. McFate, A. S. Tait, and A. Verma. 2005. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J. Biol. Chem. 280:41928–41939.
  • MacKenzie, E. D., M. A. Selak, D. A. Tennant, L. J. Payne, S. Crosby, C. M. Frederiksen, D. G. Watson, and E. Gottlieb. 2007. Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol. Cell. Biol. 27:3282–3289.
  • Makino, N., K. Sasaki, K. Hashida, and Y. Sakakura. 2004. A metabolic model describing the H2O2 elimination by mammalian cells including H2O2 permeation through cytoplasmic and peroxisomal membranes: comparison with experimental data. Biochim. Biophys. Acta 1673:149–159.
  • Mansfield, K. D., R. D. Guzy, Y. Pan, R. M. Young, T. P. Cash, P. T. Schumacker, and M. C. Simon. 2005. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell. Metab. 1:393–399.
  • Meng, Q., Y. T. Wong, J. Chen, and R. Ruan. 2007. Age-related changes in mitochondrial function and antioxidative enzyme activity in Fischer 344 rats. Mech. Ageing Dev. 128:286–292.
  • Moeller, B. J., Y. Cao, C. Y. Li, and M. W. Dewhirst. 2004. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 5:429–441.
  • Nakamura, J., E. R. Purvis, and J. A. Swenberg. 2003. Micromolar concentrations of hydrogen peroxide induce oxidative DNA lesions more efficiently than millimolar concentrations in mammalian cells. Nucleic Acids Res. 31:1790–1795.
  • Page, E. L., D. A. Chan, A. J. Giaccia, M. Levine, and D. E. Richard. 2008. Hypoxia-inducible factor-1α stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion. Mol. Biol. Cell 19:86–94.
  • Pan, Y., K. D. Mansfield, C. C. Bertozzi, V. Rudenko, D. A. Chan, A. J. Giaccia, and M. C. Simon. 2007. Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro. Mol. Cell. Biol. 27:912–925.
  • Park, S., X. You, and J. A. Imlay. 2005. Substantial DNA damage from submicromolar intracellular hydrogen peroxide detected in Hpx- mutants of Escherichia coli. Proc. Natl. Acad. Sci. USA 102:9317–9322.
  • Peters, O., T. Back, U. Lindauer, C. Busch, D. Megow, J. Dreier, and U. Dirnagl. 1998. Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat. J. Cereb. Blood Flow Metab. 18:196–205.
  • Pollard, P. J., J. J. Briere, N. A. Alam, J. Barwell, E. Barclay, N. C. Wortham, T. Hunt, M. Mitchell, S. Olpin, S. J. Moat, I. P. Hargreaves, S. J. Heales, Y. L. Chung, J. R. Griffiths, A. Dalgleish, J. A. McGrath, M. J. Gleeson, S. V. Hodgson, R. Poulsom, P. Rustin, and I. P. Tomlinson. 2005. Accumulation of Krebs cycle intermediates and over-expression of HIF1α in tumours which result from germline FH and SDH mutations. Hum. Mol. Genet. 14:2231–2239.
  • Pouyssegur, J., and F. Mechta-Grigoriou. 2006. Redox regulation of the hypoxia-inducible factor. Biol. Chem. 387:1337–1346.
  • Powell, F. L. 2003. Functional genomics and the comparative physiology of hypoxia. Annu. Rev. Physiol. 65:203–230.
  • Qutub, A. A., and A. S. Popel. 2006. A computational model of intracellular oxygen sensing by hypoxia-inducible factor HIF1 alpha. J. Cell Sci. 119:3467–3480.
  • Qutub, A. A., and A. S. Popel. 2007. Three autocrine feedback loops determine HIF1 alpha expression in chronic hypoxia. Biochim. Biophys. Acta 1773:1511–1525.
  • Schlegel, H. G. 1977. Aeration without air: oxygen supply by hydrogen peroxide. Biotechnol. Bioeng. 19:413–424.
  • Schraufstatter, I., P. A. Hyslop, J. H. Jackson, and C. G. Cochrane. 1988. Oxidant-induced DNA damage of target cells. J. Clin. Investig. 82:1040–1050.
  • Schroedl, C., D. S. McClintock, G. R. Budinger, and N. S. Chandel. 2002. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am. J. Physiol. Lung Cell Mol. Physiol. 283:L922–L931.
  • Seaver, L. C., and J. A. Imlay. 2001. Hydrogen peroxide fluxes and compartmentalization inside growing Escherichia coli. J. Bacteriol. 183:7182–7189.
  • Selak, M. A., S. M. Armour, E. D. MacKenzie, H. Boulahbel, D. G. Watson, K. D. Mansfield, Y. Pan, M. C. Simon, C. B. Thompson, and E. Gottlieb. 2005. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 7:77–85.
  • Selak, M. A., R. V. Duran, and E. Gottlieb. 2006. Redox stress is not essential for the pseudo-hypoxic phenotype of succinate dehydrogenase deficient cells. Biochim. Biophys. Acta 1757:567–572.
  • Semenza, G. L. 2004. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 19:176–182.
  • Senoo-Matsuda, N., K. Yasuda, M. Tsuda, T. Ohkubo, S. Yoshimura, H. Nakazawa, P. S. Hartman, and N. Ishii. 2001. A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J. Biol. Chem. 276:41553–41558.
  • Srinivas, V., I. Leshchinsky, N. Sang, M. P. King, A. Minchenko, and J. Caro. 2001. Oxygen sensing and HIF-1 activation does not require an active mitochondrial respiratory chain electron-transfer pathway. J. Biol. Chem. 276:21995–21998.
  • Stone, J. R., and S. Yang. 2006. Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal. 8:243–270.
  • Sumbayev, V. V., and I. M. Yasinska. 2006. Peroxynitrite as an alternative donor of oxygen in HIF-1α proline hydroxylation under low oxygen availability. Free Radic. Res. 40:631–635.
  • Szatrowski, T. P., and C. F. Nathan. 1991. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 51:794–798.
  • Szeto, S. S., S. N. Reinke, B. D. Sykes, and B. D. Lemire. 2007. Ubiquinone-binding site mutations in the Saccharomyces cerevisiae succinate dehydrogenase generate superoxide and lead to the accumulation of succinate. J. Biol. Chem. 282:27518–27526.
  • Tanriverdi, T., H. Hanimoglu, T. Kacira, G. Z. Sanus, R. Kemerdere, P. Atukeren, K. Gumustas, B. Canbaz, and M. Y. Kaynar. 2007. Glutathione peroxidase, glutathione reductase and protein oxidation in patients with glioblastoma multiforme and transitional meningioma. J. Cancer Res. Clin. Oncol. 133:627–633.
  • Teixeira, H. D., R. I. Schumacher, and R. Meneghini. 1998. Lower intracellular hydrogen peroxide levels in cells overexpressing CuZn-superoxide dismutase. Proc. Natl. Acad. Sci. USA 95:7872–7875.
  • Tuttle, S. W., A. Maity, P. R. Oprysko, A. V. Kachur, I. S. Ayene, J. E. Biaglow, and C. J. Koch. 2007. Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration: implications for the mechanism of HIF-1α stabilization under moderate hypoxia. J. Biol. Chem. 282:36790–36796.
  • Vangeison, G., D. Carr, H. J. Federoff, and D. A. Rempe. 2008. The good, the bad, and the cell type-specific roles of hypoxia inducible factor-1 alpha in neurons and astrocytes. J. Neurosci. 28:1988–1993.
  • Vaux, E. C., E. Metzen, K. M. Yeates, and P. J. Ratcliffe. 2001. Regulation of hypoxia-inducible factor is preserved in the absence of a functioning mitochondrial respiratory chain. Blood 98:296–302.
  • Vordermark, D., and J. M. Brown. 2003. Evaluation of hypoxia-inducible factor-1α (HIF-1α) as an intrinsic marker of tumor hypoxia in U87 MG human glioblastoma: in vitro and xenograft studies. Int. J. Radiat. Oncol. Biol. Phys. 56:1184–1193.
  • Wang, G. L., B. H. Jiang, E. A. Rue, and G. L. Semenza. 1995. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA 92:5510–5514.
  • Wartenberg, M., F. C. Ling, M. Muschen, F. Klein, H. Acker, M. Gassmann, K. Petrat, V. Putz, J. Hescheler, and H. Sauer. 2003. Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species. FASEB J. 17:503–505.
  • Wellman, T. L., J. Jenkins, P. L. Penar, B. Tranmer, R. Zahr, and K. M. Lounsbury. 2004. Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1α (HIF-1α) in explants of human pial arteries. FASEB J. 18:379–381.
  • Williams, N., and J. Yandell. 1982. Outer-sphere electron transfer of ascorbate anions. Aust. J. Chem. 35:1133–1144.
  • Xia, C., Q. Meng, L. Z. Liu, Y. Rojanasakul, X. R. Wang, and B. H. Jiang. 2007. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 67:10823–10830.
  • Yang, Z. Z., A. Y. Zhang, F. X. Yi, P. L. Li, and A. P. Zou. 2003. Redox regulation of HIF-1alpha levels and HO-1 expression in renal medullary interstitial cells. Am. J. Physiol. Renal Physiol. 284:F1207–F1215.
  • Yankovskaya, V., R. Horsefield, S. Tornroth, C. Luna-Chavez, H. Miyoshi, C. Leger, B. Byrne, G. Cecchini, and S. Iwata. 2003. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science 299:700–704.
  • Zhong, W., T. Yan, R. Lim, and L. W. Oberley. 1999. Expression of superoxide dismutases, catalase, and glutathione peroxidase in glioma cells. Free Radic. Biol. Med. 27:1334–1345.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.