Redox imbalance in cystine/glutamate transporter-deficient mice
Open accessAbstract
Cystine/glutamate transporter, designated as system x(-)(c), mediates cystine entry in exchange for intracellular glutamate in mammalian cells. This transporter consists of two protein components, xCT and 4F2 heavy chain, and the former is predicted to mediate the transport activity. This transporter plays a pivotal role for maintaining the intracellular GSH levels and extracellular cystine/cysteine redox balance in cultured cells. To clarify the physiological roles of this transporter in vivo, we generated and characterized mice lacking xCT. The xCT(-/-) mice were healthy in appearance and fertile. However, cystine concentration in plasma was significantly higher in these mice, compared with that in the littermate xCT(-/-) mice, while there was no significant difference in plasma cysteine concentration. Plasma GSH level in xCT(-/-) mice was lower than that in the xCT(-/-) mice. The embryonic fibroblasts derived from xCT(-/-) mice failed to survive in routine culture medium, and 2-mercaptoethanol was required for survival and growth. When 2-mercaptoethanol was removed from the culture medium, cysteine and GSH in these cells dramatically decreased, and cells started to die within 24 h. N-Acetyl cysteine also rescued xCT(-/-)-derived cells and permitted growth. These results demonstrate that system x(-)(c) contributes to maintaining the plasma redox balance in vivo but is dispensable in mammalian development, although it is vitally important to cells in vitro.
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SLC7A11-deficient mice develop normally and are healthy.
“SLC7A11-deficient mice develop normally and are healthy [79]”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [79]
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Free Radicals in the Physiological Control of Cell Function
Dröge, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00018.2001 · Cited by 9,855 · see citing works
Tietze, F. (1969) · Analytical Biochemistry · doi:10.1016/0003-2697(69)90064-5 · Cited by 6,077 · see citing works
Sato, H., Tamba, M., Ishii, T., & Bannai, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.17.11455 · Cited by 1,111 · see citing works
Self-citationRole of amino acid transport and countertransport in nutrition and metabolism.
Christensen, H. N. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.1.43 · Cited by 1,105 · see citing works
Redox state of glutathione in human plasma
Jones, D. P., Carlson, J. L., Mody, V. C., Cai, J., Lynn, M., & Sternberg, P. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00275-0 · Cited by 587 · see citing works
Sasaki, H., Sato, H., Kuriyama-Matsumura, K., Sato, K., Maebara, K., Wang, H., Tamba, M., Itoh, K., Yamamoto, M. P., & Bannai, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208704200 · Cited by 544 · see citing works
Self-citationMansoor, M. A., Svardal, A. M., & Ueland, P. M. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90456-h · Cited by 505 · see citing works
Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture.
Bannai, S., & Kitamura, E. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85901-x · Cited by 456 · see citing works
Self-citationJones, D. P., Mody, V. C., Carlson, J. L., Lynn, M. J., & Sternberg, P. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01040-7 · Cited by 392 · see citing works
Role of membrane transport in metabolism and function of glutathione in mammals
Bannai, S., & Tateishi, N. (1986) · The Journal of Membrane Biology · doi:10.1007/bf01870891 · Cited by 386 · see citing works
Self-citationTransport of cystine and cysteine in mammalian cells
Bannai, S. (1984) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(84)90014-5 · Cited by 329 · see citing works
Self-citationCotgreave, I. A., & Moldéus, P. (1986) · Journal of Biochemical and Biophysical Methods · doi:10.1016/0165-022x(86)90102-8 · Cited by 233 · see citing works
Ishii, T., Bannai, S., & Sugita, Y. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43284-x · Cited by 221 · see citing works
Self-citationOxidation of glutathione and cysteine in human plasma associated with smoking
Moriarty, S. E., Shah, J. H., Lynn, M., Jiang, S., Openo, K., Jones, D. P., & Sternberg, P. (2003) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.09.006 · Cited by 193 · see citing works
Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation
Sato, H., Nomura, S., Maebara, K., Sato, K., Tamba, M., & Bannai, S. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.10.009 · Cited by 176 · see citing works
Self-citationDistribution of Cystine/Glutamate Exchange Transporter, System xc−, in the Mouse Brain
Sato, H., Tamba, M., Okuno, S., Sato, K., Keino‐Masu, K., Masu, M., & Bannai, S. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-18-08028.2002 · Cited by 167 · see citing works
Self-citationInduction of cystine transport activity in mouse peritoneal macrophages.
Watanabe, H., & Bannai, S. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.3.628 · Cited by 161 · see citing works
Self-citationCystine Uptake and Glutathione Level in Fetal Brain Cells in Primary Culture and in Suspension
Sagara, J., Miura, K., & Bannai, S. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb09801.x · Cited by 146 · see citing works
Self-citationBannai, S. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43371-0 · Cited by 141 · see citing works
Self-citationSato, H., Fujiwara, K., Sagara, J., & Bannai, S. (1995) · Biochemical Journal · doi:10.1042/bj3100547 · Cited by 128 · see citing works
Self-citationInduction of cystine transport activity in human fibroblasts by oxygen
Bannai, S., Sato, H., Ishii, T., & Sugita, Y. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51491-5 · Cited by 121 · see citing works
Self-citationHack, V., Breitkreutz, R., Kinscherf, R., Röhrer, H., Bärtsch, P., Taut, F. J. H., Benner, A., & Dröge, W. (1998) · Blood · doi:10.1182/blood.v92.1.59.413a05_59_67 · Cited by 101 · see citing works
Wilcken, D. E. L., Gupta, V. J., & Reddy, S. G. (1980) · Clinical Science · doi:10.1042/cs0580427 · Cited by 96 · see citing works
Sato, H., Kuriyama-Matsumura, K., Hashimoto, T., Sasaki, H., Wang, H., Ishii, T., Mann, G. E., & Bannai, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007216200 · Cited by 89 · see citing works
Self-citationBannai, S., Sato, H., Ishii, T., & Taketani, S. (1991) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(91)90153-o · Cited by 87 · see citing works
Self-citationHildebrandt, W., Alexander, S., Bärtsch, P., & Dröge, W. (2002) · Blood · doi:10.1182/blood.v99.5.1552 · Cited by 85 · see citing works
Hack, V., Schmid, D., Breitkreutz, R., Stahl‐Henning, C., Brings, P., Kinscherf, R., Taut, F. J. H., Holm, E., & Dröge, W. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.1.9034170 · Cited by 68 · see citing works
Plasma cystine concentration and redox state in aging and physical exercise
Hildebrandt, W., Kinscherf, R., Hauer, K. A., Holm, E., & Dröge, W. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00013-1 · Cited by 57 · see citing works
Various forms of plasma cysteine and its metabolites in patients undergoing hemodialysis
Wlodek, P. J., Iciek, M., Miłkowski, A., & Smoleński, O. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(00)00369-7 · Cited by 35 · see citing works
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Jiang, X., Stockwell, B. R., & Conrad, M. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00324-8 · Cited by 7,698 · see citing works
Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
Stockwell, B. R., Friedmann Angeli, J. P., Bayir, H., Bush, A. I., Conrad, M., Dixon, S. J., Fulda, S., Gascón, S., Hatzios, S. K., Kagan, V. E., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.021 · Cited by 7,695 · see citing works
Ferroptosis: molecular mechanisms and health implications
Tang, D., Chen, X., Kang, R., & Kroemer, G. (2020) · Cell Research · doi:10.1038/s41422-020-00441-1 · Cited by 4,332 · see citing works
Ferroptosis: Death by Lipid Peroxidation
Yang, W. S., & Stockwell, B. R. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.10.014 · Cited by 3,088 · see citing works
Broadening horizons: the role of ferroptosis in cancer
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00462-0 · Cited by 2,938 · see citing works
Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy
Koppula, P., Zhuang, L., & Gan, B. (2020) · Protein & Cell · doi:10.1007/s13238-020-00789-5 · Cited by 2,546 · see citing works
Ferroptosis: machinery and regulation
Chen, X., Li, J., Kang, R., Klionsky, D. J., & Tang, D. (2021) · Autophagy · doi:10.1080/15548627.2020.1810918 · Cited by 2,099 · see citing works
Dixon, S. J., Patel, D. N., Welsch, M., Skouta, R., Lee, E. D., Hayano, M., Thomas, A. G., Gleason, C. E., Tatonetti, N. P., Slusher, B. S., et al. (2014) · eLife · doi:10.7554/elife.02523 · Cited by 2,088 · see citing works
Jones, D. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1865 · Cited by 1,726 · see citing works
Role of GPX4 in ferroptosis and its pharmacological implication
Seibt, T. M., Proneth, B., & Conrad, M. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.014 · Cited by 1,520 · see citing works
The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression
Lei, G., Zhang, Y., Koppula, P., Liu, X., Zhang, J., Lin, S. H., Ajani, J. A., Xiao, Q., Liao, Z., Wang, H., et al. (2020) · Cell Research · doi:10.1038/s41422-019-0263-3 · Cited by 1,318 · see citing works
Cysteine depletion induces pancreatic tumor ferroptosis in mice
Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., et al. (2020) · Science · doi:10.1126/science.aaw9872 · Cited by 1,294 · see citing works
Ishimoto, T., Nagano, O., Yae, T., Tamada, M., Motohara, T., Oshima, H., Oshima, M., Ikeda, T., Asaba, R., Yagi, H., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.01.038 · Cited by 1,192 · see citing works
Emerging Mechanisms and Disease Relevance of Ferroptosis
Stockwell, B. R., Jiang, X., & Gu, W. J. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.02.009 · Cited by 1,107 · see citing works
Zilka, O., Shah, R., Li, B., Angeli, J. P. F., Grießer, M., Conrad, M., & Pratt, D. A. (2017) · ACS Central Science · doi:10.1021/acscentsci.7b00028 · Cited by 1,052 · see citing works
The chemical basis of ferroptosis
Conrad, M., & Pratt, D. A. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0408-1 · Cited by 1,027 · see citing works
Lewerenz, J., Hewett, S. J., Huang, Y. S., Lambros, M. P., Gout, P. W., Kalivas, P. W., Massie, A., Smolders, I. J., Methner, A., Pergande, M., et al. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4391 · Cited by 996 · see citing works
Glutamate as a neurotransmitter in the healthy brain
Zhou, Y., & Danbolt, N. C. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1180-8 · Cited by 989 · see citing works
Koppula, P., Zhang, Y., Zhuang, L., & Gan, B. (2018) · 癌症：英文版 · doi:10.1186/s40880-018-0288-x · Cited by 932 · see citing works
Ferroptosis: Role of lipid peroxidation, iron and ferritinophagy
Latunde-Dada, G. O. (2017) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2017.05.019 · Cited by 892 · see citing works
Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model
Zhang, Y., Tan, H., Daniels, J. D., Zandkarimi, F., Liu, H., Brown, L. M., Uchida, K., O’Connor, O. A., & Stockwell, B. R. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.01.008 · Cited by 729 · see citing works
GPx4, Lipid Peroxidation, and Cell Death: Discoveries, Rediscoveries, and Open Issues
Maiorino, M., Conrad, M., & Ursini, F. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7115 · Cited by 709 · see citing works
The SLC3 and SLC7 families of amino acid transporters
Fotiadis, D., Kanai, Y., & Palacı́n, M. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.10.007 · Cited by 674 · see citing works
Characterization of ferroptosis in murine models of hemochromatosis
Wang, H., An, P., Xie, E., Wu, Q., Fang, X., Gao, H., Zhang, Z., Li, Y., Wang, X., Zhang, J., et al. (2017) · Hepatology · doi:10.1002/hep.29117 · Cited by 656 · see citing works
Cellular degradation systems in ferroptosis
Chen, X., Yu, C., Kang, R., Kroemer, G., & Tang, D. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00728-1 · Cited by 644 · see citing works
Conrad, M., & Sato, H. (2011) · Amino Acids · doi:10.1007/s00726-011-0867-5 · Cited by 607 · see citing works
Self-citationDixon, S. J., & Stockwell, B. R. (2018) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055844 · Cited by 588 · see citing works
Regulation of lipid peroxidation and ferroptosis in diverse species
Conrad, M., Kagan, V. E., Bayir, H., Pagnussat, G. C., Head, B., Traber, M. G., & Stockwell, B. R. (2018) · Genes & Development · doi:10.1101/gad.314674.118 · Cited by 544 · see citing works
Ferroptosis, radiotherapy, and combination therapeutic strategies
Lei, G., Mao, C., Yan, Y., Zhuang, L., & Gan, B. (2021) · Protein & Cell · doi:10.1007/s13238-021-00841-y · Cited by 518 · see citing works
Ouyang, S., Li, H., Lou, L., Huang, Q., Zhang, Z., Mo, J., Li, M., Lu, J., Zhu, K., Chu, Y., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102317 · Cited by 507 · see citing works
Bhutia, Y. D., Babu, E., Ramachandran, S., & Ganapathy, V. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3745 · Cited by 483 · see citing works
The Role of Ferroptosis in Cancer Development and Treatment Response
Lu, B., Chen, X. B., Ying, M. D., He, Q. J., Cao, J., & Yang, B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00992 · Cited by 444 · see citing works
Ono, K., Akaike, T., Sawa, T., Kumagai, Y., Wink, D. A., Tantillo, D. J., Hobbs, A. J., Nagy, P., Xian, M., Lin, J., et al. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.09.007 · Cited by 422 · see citing works
Sato, M., Kusumi, R., Hamashima, S., Kobayashi, S., Sasaki, S., Komiyama, Y., Izumikawa, T., Conrad, M., Bannai, S., & Sato, H. (2018) · Scientific Reports · doi:10.1038/s41598-018-19213-4 · Cited by 409 · see citing works
Self-citationThe x cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases
Lo, M., Wang, Y., & Gout, P. W. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21366 · Cited by 399 · see citing works
Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell
Yae, T., Tsuchihashi, K., Ishimoto, T., Motohara, T., Yoshikawa, M., Yoshida, G. J., Wada, T., Masuko, T., Mogushi, K., Tanaka, H., et al. (2012) · Nature Communications · doi:10.1038/ncomms1892 · Cited by 375 · see citing works
Ferroptosis in Cancer Cell Biology
Bebber, C. M., Müller, F., Clemente, L. P., Weber, J., & von Karstedt, S. (2020) · Cancers · doi:10.3390/cancers12010164 · Cited by 360 · see citing works
Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia
Zhang, W., Trachootham, D., Liu, J., Chen, G., Pelicano, H., Garcı́a-Prieto, C., Lu, W., Burger, J. A., Croce, C. M., Plunkett, W. K., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2432 · Cited by 357 · see citing works
Cysteine Metabolism in Neuronal Redox Homeostasis
Paul, B. D., Sbodio, J. I., & Snyder, S. H. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.02.007 · Cited by 356 · see citing works
Regulation of Neuronal Glutathione Synthesis
Aoyama, K., Watabe, M., & Nakaki, T. (2008) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08r01cr · Cited by 356 · see citing works
Ferroptosis in health and disease
Berndt, C., Alborzinia, H., Skafar, V., Ayton, S., Barayeu, U., Bartelt, A., Bayır, H., Bebber, C. M., Birsoy, K., Böttcher, J. P., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103211 · Cited by 353 · see citing works
Bayır, H., Dixon, S. J., Tyurina, Y. Y., Kellum, J. A., & Kagan, V. E. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00689-x · Cited by 346 · see citing works
Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes
Maschalidi, S., Mehrotra, P., Keçeli, B. N., Cleene, H. K. L. D., Lecomte, K., der Cruyssen, R. V., Janssen, P., Pinney, J. J., Loo, G., Elewaut, D. S., et al. (2022) · Nature · doi:10.1038/s41586-022-04754-6 · Cited by 333 · see citing works
The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death
Banjac, A., Perisic, T., Sato, H., Seiler, A., Bannai, S., Weiss, N., Kölle, P., Tschoep, K., Issels, R. D., Daniel, P. T., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1210796 · Cited by 324 · see citing works
Self-citationEmerging mechanisms and targeted therapy of ferroptosis in cancer
Wang, H., Cheng, Y., Mao, C., Liu, S., Xiao, D., Huang, J. X., & Tao, Y. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.03.022 · Cited by 320 · see citing works
Achieving Life through Death: Redox Biology of Lipid Peroxidation in Ferroptosis
Bayır, H., Anthonymuthu, T. S., Tyurina, Y. Y., Patel, S. J., Amoscato, A. A., Lamade, A. M., Yang, Q., Vladimirov, G. K., Philpott, C. C., & Kagan, V. E. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.03.014 · Cited by 318 · see citing works
Shih, A. Y., Erb, H., Sun, X., Toda, S., Kalivas, P. W., & Murphy, T. H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3178-06.2006 · Cited by 315 · see citing works
Lim, J. K. M., Delaidelli, A., Minaker, S. W., Zhang, H., Čolović, M., Yang, H., Negri, G. L., von Karstedt, S., Lockwood, W. W., Schaffer, P. C., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821323116 · Cited by 311 · see citing works
Redox regulation in stem-like cancer cells by CD44 variant isoforms
Nagano, O., Okazaki, S., & Saya, H. (2013) · Oncogene · doi:10.1038/onc.2012.638 · Cited by 279 · see citing works
Ferroptosis and Its Potential Role in Human Diseases
Han, C., Liu, Y., Dai, R., Ismail, N., Su, W., & Li, B. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00239 · Cited by 274 · see citing works
Lewerenz, J., Ates, G., Methner, A., Conrad, M., & Maher, P. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00214 · Cited by 273 · see citing works
Nishizawa, H., Matsumoto, M., Shindo, T., Saigusa, D., Kato, H., Suzuki, K., Sato, M., Ishii, Y., Shimokawa, H., & Igarashi, K. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.009548 · Cited by 273 · see citing works
The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival
Combs, J. A., & DeNicola, G. M. (2019) · Cancers · doi:10.3390/cancers11050678 · Cited by 271 · see citing works
Persister cancer cells: Iron addiction and vulnerability to ferroptosis
Rodriguez, R., Schreiber, S. L., & Conrad, M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.001 · Cited by 271 · see citing works
Ferroptosis: when metabolism meets cell death
Zheng, J., & Conrad, M. (2024) · Physiological Reviews · doi:10.1152/physrev.00031.2024 · Cited by 270 · see citing works
System xc− and Thioredoxin Reductase 1 Cooperatively Rescue Glutathione Deficiency
Mandal, P. K., Seiler, A., Perisic, T., Kölle, P., Banjac Canak, A., Förster, H., Weiss, N., Kremmer, E., Lieberman, M. W., Bannai, S., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.121327 · Cited by 269 · see citing works
Self-citationCysteine metabolic circuitries: druggable targets in cancer
Bonifácio, V. D. B., Pereira, S. A., Serpa, J., & Vicente, J. B. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01156-1 · Cited by 269 · see citing works
Tewari, B. P., Chaunsali, L., Campbell, S. L., Patel, D. C., Goode, A. E., & Sontheimer, H. (2018) · Nature Communications · doi:10.1038/s41467-018-07113-0 · Cited by 208 · see citing works
The role of Ca2+ in cell death caused by oxidative glutamate toxicity and ferroptosis
Maher, P. A., van Leyen, K., Dey, P. N., Honrath, B., Dolga, A. M., & Methner, A. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.05.007 · Cited by 208 · see citing works
Dynamic model of CHO cell metabolism
Nolan, R. P., & Lee, K. (2010) · Metabolic Engineering · doi:10.1016/j.ymben.2010.09.003 · Cited by 207 · see citing works
SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer
Lee, J., & Roh, J. (2022) · Antioxidants · doi:10.3390/antiox11122444 · Cited by 206 · see citing works
Selenium detoxification is required for cancer-cell survival
Carlisle, A. E., Lee, N., Matthew-Onabanjo, A. N., Spears, M. E., Park, S. J., Youkana, D., Doshi, M. B., Peppers, A., Li, R., Joseph, A. B., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0224-7 · Cited by 202 · see citing works
Bundel, D. D., Schallier, A., Loyens, E., Fernando, R. N., Miyashita, H., Liefferinge, J. V., Vermoesen, K., Bannai, S., Sato, H., Michotte, Y. M., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5465-10.2011 · Cited by 193 · see citing works
Self-citationDiurnal variation in glutathione and cysteine redox states in human plasma
Blanco, R. A., Ziegler, T. R., Carlson, B. A., Cheng, P., Park, Y. H., Cotsonis, G., Accardi, C. J., & Jones, D. P. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.4.1016 · Cited by 192 · see citing works
Savaskan, N. E., Heckel, A., Hahnen, E., Engelhorn, T., Doerfler, A., Ganslandt, O., Nimsky, C., Buchfelder, M., & Eyüpoglu, I. Y. (2008) · Nature Medicine · doi:10.1038/nm1772 · Cited by 192 · see citing works
Recommendations for robust and reproducible research on ferroptosis
Mishima, E., Nakamura, T., Doll, S. G., Proneth, B., Fedorova, M., Pratt, D. A., Angeli, J. P. F., Dixon, S. J., Wahida, A., & Conrad, M. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00843-2 · Cited by 191 · see citing works
Yoshikawa, M., Tsuchihashi, K., Ishimoto, T., Yae, T., Motohara, T., Sugihara, E., Onishi, N., Masuko, T., Yoshizawa, K., Kawashiri, S., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3609-t · Cited by 190 · see citing works
Hasegawa, M., Takahashi, H., Rajabi, H. N., Alam, M., Suzuki, Y., Li, Y., Tagde, A., Maeda, T., Hiraki, M., Sukhatme, V. P., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7598 · Cited by 189 · see citing works
The Glutathione System: A New Drug Target in Neuroimmune Disorders
Morris, G., Anderson, G., Dean, O. M., Berk, M., Gałecki, P., Martín-Subero, M., & Maes, M. H. J. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8705-x · Cited by 187 · see citing works
Emerging Regulatory Paradigms in Glutathione Metabolism
Liu, Y., Hyde, A. S., Simpson, M. A., & Barycki, J. J. (2014) · Advances in cancer research · doi:10.1016/b978-0-12-420117-0.00002-5 · Cited by 186 · see citing works
Liu, X., Zhang, Y., Zhuang, L., Olszewski, K. L., & Gan, B. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.11.010 · Cited by 184 · see citing works
Ishii, T., Warabi, E., & Mann, G. E. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.09.002 · Cited by 177 · see citing works
Lewerenz, J., Albrecht, P., Tien, M. T., Henke, N., Karumbayaram, S., Kornblum, H. I., Wiedau‐Pazos, M., Schubert, D., Maher, P. A., & Methner, A. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06347.x · Cited by 174 · see citing works
Lewerenz, J., & Maher, P. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807325200 · Cited by 173 · see citing works
Current approaches to enhance glutamate transporter function and expression
Fontana, A. C. K. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13200 · Cited by 171 · see citing works
Arensman, M. D., Yang, X. S., Leahy, D., Toral‐Barza, L., Mileski, M., Rosfjord, E. C., Wang, F., Deng, S., Myers, J. S., Abraham, R. T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814932116 · Cited by 171 · see citing works
Exploiting ferroptosis vulnerabilities in cancer
Nakamura, T., & Conrad, M. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01425-8 · Cited by 169 · see citing works
Cysteine, Glutathione, and Thiol Redox Balance in Astrocytes
McBean, G. J. (2017) · Antioxidants · doi:10.3390/antiox6030062 · Cited by 167 · see citing works
Amino Acid Transporters and Glutamine Metabolism in Breast Cancer
Cha, Y. J., Kim, E.-S., & Koo, J. S. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030907 · Cited by 167 · see citing works
Posttranslational Modifications in Ferroptosis
Wei, X., Yi, X., Zhu, X., & Jiang, D. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/8832043 · Cited by 165 · see citing works
Molecular and cellular mechanisms underlying brain metastasis of breast cancer
Hosonaga, M., Saya, H., & Arima, Y. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09881-y · Cited by 162 · see citing works
Glutathione and its precursors in cancer
Asantewaa, G., & Harris, I. S. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.03.001 · Cited by 158 · see citing works
Magtanong, L., & Dixon, S. J. (2018) · Developmental Neuroscience · doi:10.1159/000496922 · Cited by 155 · see citing works
Redox Regulation in the Extracellular Environment
Ottaviano, F. G., Handy, D. E., & Loscalzo, J. (2007) · Circulation Journal · doi:10.1253/circj.72.1 · Cited by 155 · see citing works
Nieoullon, A. L., Canolle, B., Masmejean, F., Guillet, B. A., Pisano, P. S., & Lortet, S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03978.x · Cited by 155 · see citing works
Francioso, A., Conrado, A. B., Mosca, L., & Fontana, M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/8294158 · Cited by 153 · see citing works
Targeting Ferroptosis: New Hope for As-Yet-Incurable Diseases
Conrad, M., Lorenz, S., & Proneth, B. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.08.010 · Cited by 151 · see citing works
Goji, T., Takahara, K., Negishi, M., & Katoh, H. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.814392 · Cited by 150 · see citing works
Excitatory Amino Acid Transporters (EAATs): Glutamate Transport and Beyond
Magi, S., Piccirillo, S., Amoroso, S., & Lariccia, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225674 · Cited by 150 · see citing works
Ferroptosis in colorectal cancer: Potential mechanisms and effective therapeutic targets
Wang, Y., Zhang, Z., Sun, W., Zhang, J., Xu, Q., Zhou, X., & Mao, L. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113524 · Cited by 141 · see citing works
Ishii, T., & Mann, G. E. (2014) · Redox Biology · doi:10.1016/j.redox.2014.04.008 · Cited by 137 · see citing works
Sharbeen, G., McCarroll, J. A., Akerman, A., Kopecky, C., Youkhana, J., Kokkinos, J., Holst, J., Boyer, C. A., Erkan, M., Goldstein, D., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-2496 · Cited by 135 · see citing works
Regulation of antioxidants in cancer
Hecht, F., Zocchi, M., Alimohammadi, F., & Harris, I. S. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.11.001 · Cited by 135 · see citing works
Molecular basis of substrate-induced permeation by an amino acid antiporter
Kowalczyk, L., Ratera, M., Paladino, A., Bartoccioni, P., Errasti‐Murugarren, E., Valencia, E., Portella, G., Bial, S., Zorzano, A., Fita, I., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018081108 · Cited by 134 · see citing works
The role of ferroptosis in lung cancer
Wu, S., Zhu, C., Tang, D., Dou, Q. P., Shen, J., & Chen, X. (2021) · Biomarker Research · doi:10.1186/s40364-021-00338-0 · Cited by 132 · see citing works
Mechanisms and regulations of ferroptosis
Zhang, X.-D., Liu, Z., Wang, M.-S., Guo, Y.-X., Wang, X., Luo, K., Huang, S., & Li, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1269451 · Cited by 131 · see citing works
Massie, A., Schallier, A., Kim, S. W., Fernando, R. N., Kobayashi, S., Beck, H., Bundel, D. D., Vermoesen, K., Bannai, S., Smolders, I. J., et al. (2010) · The FASEB Journal · doi:10.1096/fj.10-177212 · Cited by 124 · see citing works
Self-citationAmino acids in the cultivation of mammalian cells
Salazar, A., Keusgen, M., & von Hagen, J. (2016) · Amino Acids · doi:10.1007/s00726-016-2181-8 · Cited by 124 · see citing works
Glutamate transporters in the biology of malignant gliomas
Robert, S. M., & Sontheimer, H. W. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1521-z · Cited by 120 · see citing works
Ferroptosis: An emerging therapeutic opportunity for cancer
Wang, L., Chen, X., & Yan, C. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.09.005 · Cited by 118 · see citing works
- Authors
- Sato, H., Shiiya, A., Kimata, M., Maebara, K., Tamba, M., Sakakura, Y., Makino, N., Sugiyama, F., Yagami, K.-I., Moriguchi, T., Takahashi, S., & Bannai, S.
- Affiliations
- Yamagata University (JP)
- University of Tsukuba (JP)
- Ibaraki Prefectural University of Health Sciences (JP)
- Corresponding author
- Sato, Hideyo
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 280
- Issue
- 45
- Pages
- 37423-37429
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2097822945
- Cited by
- 422
- References
- 29
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 34 · 2023: 36 · 2022: 27 · 2021: 27 · 2020: 41 · 2019: 30 · 2018: 29 · 2017: 19 · 2016: 16 · 2015: 15 · 2014: 16 · 2013: 11 · 2012: 9
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Tsukuba
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- SLC7A11, system xc-, cystine transport, glutathione, redox homeostasis, cysteine, embryonic fibroblasts, 2-mercaptoethanol, N-acetylcysteine, cysteine biosynthesis
- MeSH terms
- Amino Acids, Animals, Cells, Cultured, Cystine, Female, Fibroblasts, Glutathione, Homozygote, Male, Oxidation-Reduction, Gene Deletion, Amino Acid Transport System y+, Cell Proliferation, Mice
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