Redox status in mammalian cells and stem cells during culture in vitro: Critical roles of Nrf2 and cystine transporter activity in themaintenance of redox balance

Redox Biology

Volumn 2, Issue 1, 2014, Pages 786-794

  Ishii, Tetsuro ^a   Mann, Giovanni E ^b  

^a UNIVERSITY OF TSUKUBA   (Japan)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

2 Mercaptoethanol; CD36; Cystine transporter; Embryonic stem cells; Feeder cells; Glutathione; IPS cells; Lymphocytes; Nrf2; Oxygen; XCT

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; CYSTEINE; CYSTINE; GLUTAMIC ACID; GLUTAMINASE; GLUTAMINE; GLUTATHIONE; MULTIDRUG RESISTANCE PROTEIN; OXIDIZED LOW DENSITY LIPOPROTEIN; OXYGEN; TRANSCRIPTION FACTOR NRF2; AMINO ACID TRANSPORTER; CD36 ANTIGEN; MERCAPTOETHANOL;

AMINO ACID TRANSPORT; CELL CULTURE; CELL DIFFERENTIATION; CELL PROLIFERATION; FIBROBLAST; HUMAN; IN VITRO STUDY; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MAMMAL CELL; MEMBRANE TRANSPORT; NONHUMAN; OXIDATION REDUCTION STATE; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STABILITY; REVIEW; STEM CELL; UPREGULATION; ANIMAL; CYTOLOGY; LYMPHOCYTE; METABOLISM; LYMPHOID CELL; STEM CELL CULTURE; T LYMPHOCYTE; TRANSCRIPTION INITIATION; TRANSCRIPTION REGULATION;

ACTIVATING TRANSCRIPTION FACTOR 4; AMINO ACID TRANSPORT SYSTEMS, ACIDIC; ANIMALS; ANTIGENS, CD36; CYSTINE; GLUTATHIONE; HUMANS; LYMPHOCYTES; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; STEM CELLS;

MAMMALIA;

EID: 84903202158     PISSN: 22132317     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.redox.2014.04.008     Document Type: Review

References (68)

1. Chen C., Hirsch J.G. The effects of mercaptoethanol and of peritoneal macrophages on the antibody-forming capacity of nonadherent mouse spleen cells in vitro. Journal of Experimental Medicine 1972, 136:604-617. http://www.ncbi.nlm.nih.gov/pubmed/4559193, 10.1084/jem.136.3.604.
2. Gorczynski R.M., Macrae S. Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors. III. Induction of T-cell activities by growth of bone marrow on feeder layers prepared from mouse thymocytes. Immunology 1979, 38:1-12. http://www.ncbi.nlm.nih.gov/pubmed/315913.
3. Epstein A.L., Kaplan H.S. Feeder layer and nutritional requirements for the establishment and cloning of human malignant lymphoma cell lines. Cancer Research 1979, 39:1748-1759. http://www.ncbi.nlm.nih.gov/pubmed/371794.
4. Broome J.D., Jeng M.W. Promotion of replication in lymphoid cells by specific thiols and disulfides in vitro. Effects on mouse lymphoma cells in comparison with splenic lymphocytes. Journal of Experimental Medicine 1973, 138:574-592. http://www.ncbi.nlm.nih.gov/pubmed/4727914, 10.1084/jem.138.3.574.
5. Oshima R. Stimulation of the clonal growth and differentiation of feeder layer dependent mouse embryonal carcinoma cells by β-mercaptoethanol. Differentiation: Research in Biological Diversity 1978, 11:149-155. http://www.ncbi.nlm.nih.gov/pubmed/720785, 10.1111/j.1432-0436.1978.tb00978.x.
6. Löwenberg B., Dicke K.A. Induction of proliferation of haemopoietic stem cells in culture. Experimental Hematology 1977, 5:319-331. http://www.ncbi.nlm.nih.gov/pubmed/891671.
7. Andrade P.Z., Santos F.D., Cabral J.M., da Silva C.L. Stem cell bioengineering strategies to widen the therapeutic applications of haematopoietic stem/progenitor cells from umbilical cord blood. Journal of Tissue Engineering and Regenerative Medicine 2013, http://www.ncbi.nlm.nih.gov/pubmed/23564692, 10.1002/term.1741.
8. Unger C., Skottman H., Blomberg P., Dilber M.S., Hovatta O. Good manufacturing practice and clinical-grade human embryonic stem cell lines. Human Molecular Genetics 2008, 17:R48-R53. http://www.ncbi.nlm.nih.gov/pubmed/18632697, 10.1093/hmg/ddn079.
9. Chen G., Gulbranson D.R., Hou Z., Bolin J.M., Ruotti V., Probasco M.D., Smuga-Otto K., Howden S.E., Diol N.R., Propson N.E., Wagner R., Lee G.O., Antosiewicz-Bourget J., Teng J.M.C., Thomson J.A. Chemically defined conditions for human iPSC derivation and culture. Nature Methods 2011, 8:424-429. http://www.ncbi.nlm.nih.gov/pubmed/21478862, 10.1038/nmeth.1593.
10. Crocco M.C., Fratnz N., Bos-Mikich A. Substrates and supplements for hESCs:a critical review. Journal of Assisted Reproduction and Genetics 2013, 30:315-323. http://www.ncbi.nlm.nih.gov/pubmed/23288664, 10.1007/s10815-012-9914-8.
11. Yamasaki S., Taguchi Y., Shimamoto A., Mukasa H., Tahara H., Okamoto T. Generation of human induced pluripotent stem (iPS) cells in serum- and feeder-free defined culture and TGF-β1 regulation of pluripotency. PLoS One 2014, 9:e87151. http://www.ncbi.nlm.nih.gov/pubmed/24489856, 10.1371/journal.pone.0087151.
12. Bannai S., Tsukeda H., Okumura H. Effect of antioxidants on cultured human diploid fibroblasts exposed to cystine-free medium. Biochemical and Biophysical Research Communications 1977, 74:1582-1588. http://www.ncbi.nlm.nih.gov/pubmed/843380, 10.1016/0006-291X(77)90623-4.
13. Ishii T., Bannai S. The synergistic action of the copper chelator bathocuproine sulphonate and cysteine in enhancing growth of L1210 cells in vitro. Journal of Cellular Physiology 1985, 125:151-155. http://www.ncbi.nlm.nih.gov/pubmed/4044667, 10.1002/jcp.1041250119.
14. Bannai S., Kitamura E. Transport interaction of L-cystine and L-glutamate in human diploid fibroblasts in culture. Journal of Biological Chemistry 1980, 255:2372-2376. http://www.ncbi.nlm.nih.gov/pubmed/7358676.
15. Bannai S. Transport of cystine and cysteine in mammalian cells. Biochimica et Biophysica Acta 1984, 779:289-306. http://www.ncbi.nlm.nih.gov/pubmed/6383474.
16. Bannai S., Ishii T. Formation of sulfhydryl groups in the culture medium by human diploid fibroblasts. Journal of Cellular Physiology 1980, 104:215-223. http://www.ncbi.nlm.nih.gov/pubmed/7410490, 10.1002/jcp.1041040211.
17. Hishinuma I., Ishii T., Watanabe H., Bannai S. Mouse lymphoma L1210 cells acquire a new cystine transport activity upon adaptation in vitro. In Vitro Cellular and Developmental Biology: Journal of the Tissue Culture Association 1986, 22:127-134. http://www.ncbi.nlm.nih.gov/pubmed/2869021, 10.1007/BF02623499.
18. Ishii T., Sugita Y., Bannai S. Regulation of glutathione levels in mouse spleen lymphocytes by transport of cysteine. Journal of Cellular Physiology 1987, 133:330-336. http://www.ncbi.nlm.nih.gov/pubmed/3680392, 10.1002/jcp.1041330217.
19. Ishii T., Hishinuma I., Bannai S., Sugita Y. Mechanism of growth promotion of mouse lymphoma L1210 cells in vitro by feeder layer or 2-mercaptoethanol. Journal of Cellular Physiology 1981, 107:283-293. 10.1002/jcp.1041070215.
20. Ishii T., Itoh K., Takahashi S., Sato H., Yanagawa T., Katoh Y., Bannai S., Yamamoto M. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. Journal of Biological Chemistry 2000, 275:16023-16029. http://www.ncbi.nlm.nih.gov/pubmed/10821856, 10.1074/jbc.275.21.16023.
21. Ishii T., Itoh K., Ruiz E., Leake D.S., Unoki H., Yamamoto M., Mann G.E. Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circulation Research 2004, 94:609-616. http://www.ncbi.nlm.nih.gov/pubmed/14752028, 10.1161/01.RES.0000119171.44657.45.
22. Bannai S., Tateishi N. Role of membrane transport in metabolism and function of glutathione in mammals. Journal of Membrane Biology 1986, 89:1-8. http://www.ncbi.nlm.nih.gov/pubmed/2870192, 10.1007/BF01870891.
23. Bannai S. Exchange of cystine and glutamate across plasma membrane of human fibroblasts. Journal of Biological Chemistry 1986, 261:2256-2263. http://www.ncbi.nlm.nih.gov/pubmed/2868011.
24. Christensen H.N. Distinguishing amino acid transport systems of a given cell or tissue. Methods in Enzymology 1989, 173:576-616. http://www.ncbi.nlm.nih.gov/pubmed/2674620, 10.1016/S0076-6879(89)73040-8.
25. Fotiadis D., Kanai Y., Palacin M. The SLC3 and SLC7 families of amino acid transporters. Molecular Aspects of Medicine 2013, 34:139-158. http://www.ncbi.nlm.nih.gov/pubmed/23506863, 10.1016/j.mam.2012.10.007.
26. Hundal H.S., Taylor P.M. Amino acid transceptors: gate keepers of nutrient exchange and regulators of nutrient signaling. American Journal of Physiology: Endocrinology and Metabolism 2009, 296:E603-E613. http://www.ncbi.nlm.nih.gov/pubmed/19158318, 10.1152/ajpendo.91002.2008.
27. Sato H., Watanabe H., Ishii T., Bannai S. Neutral amino acid transport in mouse peritoneal macrophages. Journal of Biological Chemistry 1987, 262:13015-13019. http://www.ncbi.nlm.nih.gov/pubmed/3115975.
28. Sato H., Tamba M., Ishii T., Bannai S. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. Journal of Biological Chemistry 1999, 274:11455-11458. http://www.ncbi.nlm.nih.gov/pubmed/10206947, 10.1074/jbc.274.17.11455.
29. Ballatori N., Krance S.M., Marchan R., Hammond C.L. Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Molecular Aspects of Medicine 2009, 30:13-28. http://www.ncbi.nlm.nih.gov/pubmed/18786560, 10.1016/j.mam.2008.08.004.
30. Bannai S., Ishii T. A novel function of glutamine in cell culture: utilization of glutamine for the uptake of cystine in human fibroblasts. Journal of Cellular Physiology 1988, 137:360-366. http://www.ncbi.nlm.nih.gov/pubmed/2903864, 10.1002/jcp.1041370221.
31. - in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxidants and Redox Signaling 2013, 18:522-555. 10.1089/ars.2011.4391.
32. Sato H., Tamba M., Okuno S., Sato K., Keino-Masu K., Masu M., Bannai S. Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain. Journal of Neuroscience: The Official Journal of the Society for Neuroscience 2002, 22:8028-8033. http://www.ncbi.nlm.nih.gov/pubmed/12223556.
33. Kim J.Y., Kanai Y., Chairoungdua A., Cha S.H., Matsuo H., Kim D.K., Inatomi J., Sawa H., Ida Y., Endou H. Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. Biochimica et Biophysica Acta 2001, 1512:335-344. http://www.ncbi.nlm.nih.gov/pubmed/11406111, 10.1016/S0005-2736(01)00338-8.
34. Sato H., Shiiya A., Kimata M., Maebara K., Tamba M., Sakakura Y., Makino N., Sugiyama F., Yagami K., Moriguchi T., Takahashi S., Bannai S. Redox imbalance in cystine/glutamate transporter-deficient mice. Journal of Biological Chemistry 2005, 280:37423-37429. http://www.ncbi.nlm.nih.gov/pubmed/16144837, 10.1074/jbc.M506439200.
35. Ishii T., Bannai S., Sugita Y. Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine. Journal of Biological Chemistry 1981, 256:12387-12392. http://www.ncbi.nlm.nih.gov/pubmed/7298664.
36. - in mouse T cells. Immunology Letters 2009, 125:137-144. http://www.ncbi.nlm.nih.gov/pubmed/19576933, 10.1016/j.imlet.2009.06.011.
37. Bannai S., Kitamura E. Adaptive enhancement of cystine and glutamate uptake in human diploid fibroblasts in culture. Biochimica et Biophysica Acta 1982, 721:1-10. http://www.ncbi.nlm.nih.gov/pubmed/6127114, 10.1016/0167-4889(82)90017-9.
38. Bannai S. Induction of cystine and glutamate transport activity in human fibroblasts by diethyl maleate and other electrophilic agents. Journal of Biological Chemistry 1984, 259:2435-2440. http://www.ncbi.nlm.nih.gov/pubmed/6142042.
39. Watanabe H., Bannai S. Induction of cystine transport activity in mouse peritoneal macrophages. Journal of Experimental Medicine 1987, 165:628-640. http://www.ncbi.nlm.nih.gov/pubmed/2880923, 10.1084/jem.165.3.628.
40. Bannai S., Sato H., Ishii T., Sugita Y. Induction of cystine transport activity in human fibroblasts by oxygen. Journal of Biological Chemistry 1989, 264:18480-18484. http://www.ncbi.nlm.nih.gov/pubmed/2808385.
41. Sato H., Nomura S., Maebara K., Sato K., Tamba M., Bannai S. Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation. Biochemical and Biophysical Research Communications 2004, 325:109-116. http://www.ncbi.nlm.nih.gov/pubmed/15522208, 10.1016/j.bbrc.2004.10.009.
42. Ogawa Y., Saito Y., Nishio K., Yoshida Y., Ashida H., Niki E. γ-Tocopheryl quinone, not α-tocopheryl quinone, induces adaptive response through up-regulation of cellular glutathione and cysteine availability via activation of ATF4. Free Radical Research 2008, 42:674-687. http://www.ncbi.nlm.nih.gov/pubmed/18654882, 10.1080/10715760802277396.
43. Itoh K., Chiba T., Takahashi S., Ishii T., Igarashi K., Katoh Y., Oyake T., Hayashi N., Satoh K., Hatayama I., Yamamoto M., Nabeshima Y. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochemical and Biophysical Research Communications 1997, 236:313-322. http://www.ncbi.nlm.nih.gov/pubmed/9240432, 10.1006/bbrc.1997.6943.
44. Ishii T., Warabi E., Siow R.C., Mann G.E. Sequestosome1/p62:a regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth. Free Radical Biology and Medicine 2013, 65:102-116. http://www.ncbi.nlm.nih.gov/pubmed/23792273.
45. Moscat J., Diaz-Meco M.T., Wooten M.W. Signal integration and diversification through the p62 scaffold protein. Trends in Biochemical Sciences 2007, 32:95-100. http://www.ncbi.nlm.nih.gov/pubmed/17174552, 10.1016/j.tibs.2006.12.002.
46. Dinkova-Kostova A.T., Holtzclaw W.D., Cole R.N., Itoh K., Wakabayashi N., Katoh Y., Yamamoto M., Talalay P. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences of the United States of America 2002, 99:11908-11913. http://www.ncbi.nlm.nih.gov/pubmed/12193649, 10.1073/pnas.172398899.
47. Chapple S.J., Cheng X., Mann G.E. Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease. Redox Biology 2013, 1:319-331. http://www.ncbi.nlm.nih.gov/pubmed/24024167, 10.1016/j.redox.2013.04.001.
48. Li A.C., Glass C.K. The macrophage foam cell as a target for therapeutic intervention. Nature Medicine 2002, 8:1235-1242. http://www.ncbi.nlm.nih.gov/pubmed/12411950, 10.1038/nm1102-1235.
49. Glass C.K., Witztum J.L. Atherosclerosis. The road ahead. Cell 2001, 104:503-516. http://www.ncbi.nlm.nih.gov/pubmed/11239408, 10.1016/S0092-8674(01)00238-0.
50. Sato H., Takenaka Y., Fujiwara K., Yamaguchi M., Abe K., Bannai S. Increase in cystine transport activity and glutathione level in mouse peritoneal macrophages exposed to oxidized low-density lipoprotein. Biochemical and Biophysical Research Communications 1995, 215:154-159. http://www.ncbi.nlm.nih.gov/pubmed/7575584, 10.1006/bbrc.1995.2446.
51. Siow R.C., Sato H., Leake D.S., Pearson J.D., Bannai S., Mann G.E. Vitamin C protects human arterial smooth muscle cells against atherogenic lipoproteins: Effects of antioxidant vitamins C and E on oxidized LDL-induced adaptive increase in cystine transport and glutathione. Arteriosclerosis, Thrombosis, and Vascular Biology 1998, 18:1662-1670. 10.1161/01.ATV.18.10.1662.
52. Moellering D.R., Levonen A.L., Go Y.M., Patel R.P., Dickinson D.A., Forman H.J., Darley-Usmar V.M. Induction of glutathione synthesis by oxidized low-density lipoprotein and 1-palmitoyl-2-arachidonyl phosphatidylcholine: protection against quinone-mediated oxidative stress. Biochemical Journal 2002, 362:51-59. http://www.ncbi.nlm.nih.gov/pubmed/11829739, 10.1042/0264-6021:3620051.
53. Bea F., Hudson F.N., Chait A., Kavanagh T.J., Rosenfeld M.E. Induction of glutathione synthesis in macrophages by oxidized low-density lipoproteins is mediated by consensus antioxidant response elements. Circulation Research 2003, 92:386-393. http://www.ncbi.nlm.nih.gov/pubmed/12600891, 10.1161/01.RES.0000059561.65545.16.
54. Maruyama A., Tsukamoto S., Nishikawa K., Yoshida A., Harada N., Motojima K., Ishii T., Nakane A., Yamamoto M., Itoh K. Nrf2 regulates the alternative first exons of CD36 in macrophages through specific antioxidant response elements. Archives of Biochemistry and Biophysics 2008, 477:139-145. http://www.ncbi.nlm.nih.gov/pubmed/18585365, 10.1016/j.abb.2008.06.004.
55. Sussan T.E., Jun J., Thimmulappa R., Bedja D., Antero M., Gabrielson K.L., Polotsky V.Y., Biswal S. Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice. PloS One 2008, 3:e3791. http://www.ncbi.nlm.nih.gov/pubmed/19023427, 10.1371/journal.pone.0003791.
56. Barajas B., Che N., Yin F., Rowshanrad A., Orozco L.D., Gong K.W., Wang X., Castellani L.W., Reue K., Lusis A.J., Araijo J.A. NF-E2-related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection. Arteriosclerosis, Thrombosis, and Vascular Biology 2011, 31:58-66. http://www.ncbi.nlm.nih.gov/pubmed/20947826, 10.1161/ATVBAHA.110.210906.
57. Matsumoto K., Hirano K., Nozaki S., Takamoto A., Nishida M., Nakagawa-Toyama Y., Janabi M.Y., Ohya T., Yamashita S., Matsuzawa Y. Expression of macrophage (Mphi) scavenger receptor, CD36, in cultured human aortic smooth muscle cells in association with expression of peroxisome proliferator activated receptor-gamma, which regulates gain of Mphi-like phenotype in vitro, and its implication in atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology 2000, 20:1027-1032. http://www.ncbi.nlm.nih.gov/pubmed/10764668, 10.1161/01.ATV.20.4.1027.
58. Alary J., Gueraud F., Cravedi J.P. Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways. Molecular Aspects of Medicine 2003, 24:177-187. http://www.ncbi.nlm.nih.gov/pubmed/12892995, 10.1016/S0098-2997(03)00012-8.
59. Mehrasa R., Vaziri H., Oodi A., Khorshidfar M., Golpour M., Amirizadeh N. Mesenchymal stem cells as a feeder layer can prevent apoptosis of expanded hematopoietic stem cells derived from cord blood. International Journal of Molecular and Cellular Medicine 2014, 3:1-10. http://www.ncbi.nlm.nih.gov/pubmed/24551815.
60. NIH home page stem cell information. http://stemcells.nih.gov/research/nihresearch/scunit/pages/feederfree.aspx.
61. Woodbury M.E., Ikezu T. Fibroblast growth factor-2 signaling in neurogenesis and neurodegeneration. Journal of Neuroimmune Pharmacology: The Official Journal of the Society on NeuroImmune Pharmacology 2014, 9(2):92-101. http://www.ncbi.nlm.nih.gov/pubmed/24057103.
62. Liu M.H., Tang Z.H., Li G.H., Qu S.L., Zhang Y., Ren Z., Liu L.S., Jiang Z.S. Janus-like role of fibroblast growth factor 2 in arteriosclerotic coronary artery disease: atherogenesis and angiogenesis. Atherosclerosis 2013, 229:10-17. http://www.ncbi.nlm.nih.gov/pubmed/23578358, 10.1016/j.atherosclerosis.2013.03.013.
63. Haley E.M., Kim Y. The role of basic fibroblast growth factor in glioblastoma multiforme and glioblastoma stem cells and in their in vitro culture. Cancer Letters 2014, 346:1-5. http://www.ncbi.nlm.nih.gov/pubmed/24333730, 10.1016/j.canlet.2013.12.003.
64. Malabanan K.P., Kanellakis P., Bobik A., Khachigian L.M. Activation transcription factor-4 induced by fibroblast growth factor-2 regulates vascular endothelial growth factor-A transcription in vascular smooth muscle cells and mediates intimal thickening in rat arteries following balloon injury. Circulation Research 2008, 103:378-387. http://www.ncbi.nlm.nih.gov/pubmed/18617696, 10.1161/CIRCRESAHA.107.168682.
65. Fei Y., Xiao L., Hurley M.M. Fibroblast growth factor 2 positively regulates expression of activating transcription factor 4 in osteoblasts. Biochemical and Biophysical Research Communications 2010, 391:335-339. http://www.ncbi.nlm.nih.gov/pubmed/19913500, 10.1016/j.bbrc.2009.11.059.
66. Hou J.G., Cohen G., Mytilineou C. Basic fibroblast growth factor stimulation of glial cells protects dopamine neurons from 6-hydroxydopamine toxicity: involvement of the glutathione system. Journal of Neurochemistry 1997, 69:76-83. http://www.ncbi.nlm.nih.gov/pubmed/9202296.
67. Gualtieri A.F., Mazzone G.L., Rey R.A., Schteingart H.F. FSH and bFGF stimulate the production of glutathione in cultured rat Sertoli cells. International Journal of Andrology 2009, 32:218-225. http://www.ncbi.nlm.nih.gov/pubmed/18042181, 10.1111/j.1365-2605.2007.00836.x.
68. Liu X., Albano R., Lobner D. FGF-2 induces neuronal death through upregulation of system xc-. Brain Research 2014, 1547:25-33. http://www.ncbi.nlm.nih.gov/pubmed/24374066, 10.1016/j.brainres.2013.12.018.