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Review Article

Managing odds in stem cells: insights into the role of mitochondrial antioxidant enzyme MnSOD

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Pages 570-584 | Received 24 Jan 2016, Accepted 15 Feb 2016, Published online: 28 Mar 2016

References

  • Warburg O. On the origin of cancer cells. Science 1956;123:309–314.
  • Gogvadze V, Zhivotovsky B, Orrenius S. The Warburg effect and mitochondrial stability in cancer cells. Mol Aspects Med 2010;31:60–74.
  • Kobayashi CI, Suda T. Regulation of reactive oxygen species in stem cells and cancer stem cells. J Cell Physiol 2012;227:421–430.
  • Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol 2014;15:411–421.
  • Han D, Williams E, Cadenas E. Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. Biochem J 2001;353:411–416.
  • Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol (Lond) 2003;552:335–344.
  • Hachisuka H, Dusting GJ, Abberton KM, Morrison WA, Jiang F. Role of NADPH oxidase in tissue growth in a tissue engineering chamber in rats. J Tissue Eng Regen Med 2008;2:430–435.
  • Miriyala S, Holley AK, St. Clair DK. Mitochondrial superoxide dismutase – signals of distinction. Anticancer Agents Med Chem 2011;11:181–190.
  • Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 2002;33:337–349.
  • Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev 1979;59:527–605.
  • Bordo D, Djinovic K, Bolognesi M. Conserved patterns in the Cu,Zn superoxide dismutase family. J Mol Biol 1994;238:366–386.
  • Valentine JS, Hart J. Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2003;100:3617–3622.
  • Karumbayaram S, Kelly TK, Paucar AA, Roe AJT, Umbach JA, Charles A, et al. Human embryonic stem cell-derived motor neurons expressing SOD1 mutants exhibit typical signs of motor neuron degeneration linked to ALS. Disease Models Mech 2009;2:189–195.
  • Wada T, Goparaju SK, Tooi N, Aiba K. Amyotrophic lateral sclerosis model derived from human embryonic stem cells overexpressing mutant superoxide dismutase. Stem Cells Transl Med 2012;1:396–402.
  • Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet 1996;13:43–47.
  • Ho YS, Gargano M, Cao J, Bronson RT, Heimler I, Hutz RJ. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem 1998;273:7765–7769.
  • Sheshadri P, Ashwini A, Jahnavi S, Bhonde R, Prasanna J, Kumar A. Novel role of mitochondrial manganese superoxide dismutase in STAT3 dependent pluripotency of mouse embryonic stem cells. Sci Rep 2015;5:9516–9527.
  • Marklund, SL. Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci USA 1982;79:7634–7638.
  • Marklund SL, Holme E, Hellner L. Superoxide dismutase in extracellular fluids. Clin Chim Acta 1982;126:41–51.
  • Marklund SL, Bjelle A, Elmqvist LG. Superoxide dismutase isoenzymes of the synovial fluid in rheumatoid arthritis and in reactive arthritides. Ann Rheum Dis 1986;45:847–851.
  • Sentman ML, Granström M, Jakobson H, Reaume A, Basu S, Marklund SL. Phenotypes of mice lacking extracellular superoxide dismutase and copper- and zinc-containing superoxide dismutase. J Biol Chem 2006;281:6904–6909.
  • Takahashi H, Suzuki T, Shirai A, Matsuyama A, Dohmae N, Yoshida M. Mitochondrial localization of fission yeast manganese superoxide dismutase is required for its lysine acetylation and for cellular stress resistance and respiratory growth. Biochem Biophys Res Commun 2011;406:42–46.
  • Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 1995;11:376–381.
  • Lebovitz RM, Zhang H, Vogel H, Cartwright J Jr, Dionne L, Lu N, et al. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci USA 1996;93:9782–9787.
  • Yant LJ, Ran Q, Rao L, Van Remmen H, Shibatani T, Belter JG, et al. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med 2003;34:496–502.
  • Jakupoglu C, Przemeck GK, Schneider M, Moreno SG, Mayr N, Hatzopoulos AK, et al. Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development. Mol Cell Biol 2005;25:1980–1988.
  • Conrad M, Jakupoglu C, Moreno SG, Lippl S, Banjac A, Schneider M, et al. Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. Mol Cell Biol 2004;24:9414–9423.
  • Ho YS, Xiong Y, Ma W, Spector A, Ho DS. Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem 2004;279:32804–32812.
  • Hamilton RT, Walsh ME, Van Remmen H. Mouse models of oxidative stress indicate a role for modulating healthy aging. J Clin Exp Pathol 2012;pii:005. DOI: 10.4172/2161-0681.S4-005.
  • Rosenblum JS, Gilula NB, Lerner RA. On signal sequence polymorphisms and diseases of distribution. Proc Natl Acad Sci USA 1996;93:4471–4473.
  • Van Landeghem GF, Tabatabaie P, Beckman G, Beckman L, Andersen PM. Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease. Eur J Neurol 1999;6:639–644.
  • Mitrunen K, Sillanpaa P, Kataja V, Eskelinen M, Kosma VM, Benhamou S, et al. Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis 2001;22:827–829.
  • Zhao Y, Xue Y, Oberley TD, Kiningham KK, Lin SM, Yen HC, et al. Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. Cancer Res 2001;61:6082–6088.
  • Oberley LW. Anticancer therapy by overexpression of superoxide dismutase. Antioxid Redox Signal 2001;3:461–472.
  • Skrzycki M, Czeczot H. Superoxide dismutase as a potential therapeutic agent. Adv Clin Exp Med 16:561–568.
  • Wan XS, Devalaraja MN, St. Clair DK. Molecular structure and organization of the human manganese superoxide dismutase gene. DNA Cell Biol 1994;13:1127–1136.
  • Abreu IA, Cabelli DE. Superoxide dismutases – a review of the metal-associated mechanistic variations. Biochim Biophys Acta 2010;1804:263–274.
  • Cadet J, Loft S, Olinski R, Evans MD, Bialkowski K, Richard Wagner J, et al. Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids. Free Radic Res 2012;46:367–381.
  • Bull C, Niederboffe EC, Yoshida T, Fee JA. Kinetic studies of superoxide dismutases: properties of the manganese-containing protein from Thermusthermophilus. J Am Chem Soc 1991;113:4069–4076.
  • Hunter T, Ikebukuro K, Bannister WH, Bannister JV, Hunter GJ. The conserved residue tyrosine 34 is essential for maximal activity of iron-superoxide dismutase from Escherichia coli. Biochemistry 1997;36:4925–4933.
  • Edwards RA, Baker HM, Whittaker MM, Jameson GB, Baker EN. Crystal structure of Escherichia coli manganese superoxide dismutase at 2.1-angstrom resolution. J Biol Inorg Chem 1998;3:161–171.
  • Bakthavatchalu V, Dey S, Xu Y, Jungsuwadee P, Holley AK, Dhar SK, et al. Manganese superoxide dismutase is a mitochondrial fidelity protein that protects polγ against UV-induced inactivation. Oncogene 2012;31:2129–2139.
  • Viña J, Lloret A, Ortí R, Alonso D. Molecular bases of the treatment of Alzheimer’s disease with antioxidants: prevention of oxidative stress. Mol Aspects Med 2004;25:117–123.
  • Cantin AA. Potential for antioxidant therapy of cystic fibrosis. Curr Opin Pulm Med 2004;10:531–536.
  • Seril DN, Liao J, Yang GY, Yang CS. Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 2003;24:353–362.
  • Berger MM. Can oxidative damage be treated nutritionally? Clin Nutr 2005;24:172–183.
  • Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004;84:1381–1478.
  • Lynn S, Huang EJ, Elchuri S, Naeemuddin M, Nishinaka Y, Yodoi J, et al. Selective neuronal vulnerability and inadequate stress response in superoxide dismutase mutant mice. Free Radic Biol Med 2005;38:817–828.
  • Keller JN, Kindy MS, Holtsberg FW, St Clair DK, Yen H-C, Germeyer A, et al. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci 1998;18:687–697.
  • Li Y, Copin JC, Reola LF, Calagui G, Gobbel GT, Chen SF, et al. Reduced mitochondrial manganese-superoxide dismutase activity exacerbates glutamate toxicity in cultured mouse cortical neurons. Brain Res 1998;814:164–170.
  • Ikegami T, Suzuki Y, Shimizu T, Isono K, Koseki H, Shirasawa T. Model mice for tissue-specific deletion of the manganese superoxide dismutase (MnSOD) gene. Biochem Biophys Res Commun 2002;296:729–736.
  • Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR, et al. A lifelong reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genom 2003;16:29–37.
  • Masini E, Cuzzocrea S, Mazzon E, Marzocca C, Mannaioni PF, Salvemini D. Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischemia and reperfusion injury in vivo. Br J Pharmocol 2002;136:905–917.
  • Bresciani G, Cruz IB, de Paz JA, Cuevas MJ, González-Gallego J. The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors. Free Radic Res 2013;47:781–792.
  • Soini Y, Vakkala M, Kahlos K, Pääkkö P, Kinnula V. MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than in in situ carcinomas or non-neoplastic breast epithelial cells. J Pathol 2001;195:156–162.
  • Chuang TC, Liu JY, Lin CT, Tang YT, Yeh MH, Chang SC, et al. Human manganese superoxide dismutase suppresses HER2/neu-mediated breast cancer malignancy. FEBS Lett 2007;581:4443–4449.
  • Cullen JJ, Weydert C, Hinkhouse MM, Ritchie J, Domann FE, Spitz D, et al. The role of manganese superoxide dismutase in the growth of pancreatic adenocarcinoma. Cancer Res 2003;63:1297–1303.
  • Hu Y, Rosen DG, Zhou Y, Feng L, Yang G, Liu J, et al. Mitochondrial manganese-superoxide dismutase expression in ovarian cancer: role in cell proliferation and response to oxidative stress. J Biol Chem 2005;280:39485–39492.
  • Liu R, Oberley TD, Oberley LW. Transfection and expression of MnSOD cDNA decreases tumor malignancy of human oral squamous carcinoma SCC-25 cells. Human Gene Ther 1997;8:585–595.
  • Venkataraman S, Jiang X, Weydert C. Manganese superoxide dismutase overexpression inhibits the growth of androgen-independent prostate cancer cells. Oncogene 2005;24:77–89.
  • Cullen JJ, Mitros FA, Oberley LW. Expression of antioxidant enzymes in diseases of the human pancreas: another link between chronic pancreatitis and pancreatic cancer. Pancreas 2003;26:23–27.
  • Behrend L, Mohr A, Dick T, Zwacka RM. Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells. Mol Cell Biol 2005;25:7758–7769.
  • Ridnour LA, Oberley TD, Oberley LW. Tumor suppressive effects of MnSOD overexpression may involve imbalance in peroxide generation versus peroxide removal. Antioxid Redox Signal 2004;6:501–512.
  • Oberley LW. Mechanism of the tumor suppressive effect of MnSOD overexpression. Biomed Pharmacother 2005;59:143–148.
  • Stclair D, Wan X, Kuroda M, Vichitbandha S, Tsuchida E, Urano M. Suppression of tumor metastasis by manganese superoxide dismutase is associated with reduced tumorigenicity and elevated fibronectin. Oncol Rep 1997;4:753–757.
  • Dean DC, Bowlus CL, Bourgeois S. Cloning and analysis of the promotor region of the human fibronectin gene. Proc Natl Acad Sci USA 1987;84:1876–1880.
  • Wang M, Kirk JS, Venkataraman S, Domann FE, Zhang HJ, Schafer FQ, et al. Manganese superoxide dismutase suppresses hypoxic induction of hypoxia-inducible factor-1alpha and vascular endothelial growth factor. Oncogene 2005;24:8154–8166.
  • Bonello S, Zähringer C, BelAiba RS. Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site. Arterioscler Thromb Vasc Biol 2007;27:755–761.
  • Hempel N, Carrico PM, Melendez JA. Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis. Anticancer Agents Med Chem 2011;11:191–201.
  • Behrend L, Mohr A, Dick T, Zwacka RM. Manganese superoxide dismutase induces p53-dependent senescence in colorectal cancer cells. Mol Cell Biol 2005;25:7758–7769.
  • Zhao Y, Oberley TD, Chaiswing L, Lin SM, Epstein CJ, Huang TT, et al. Manganese superoxide dismutase deficiency enhances cell turnover via tumor promoter-induced alterations in AP-1 and p53-mediated pathways in a skin cancer model. Oncogene 2002;21:3836–3846.
  • Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D, et al. Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta 2012;1822:794–814.
  • van de Wetering CI, Coleman MC, Spitz DR, Smith BJ, Knudson CM. Manganese superoxide dismutase gene dosage affects chromosomal instability and tumor onset in a mouse model of T cell lymphoma. Free Rad Biol Med 2008;44:1677–1686.
  • Joksic G, Pajovic SB, Stankovic M, Pejic S, Kasapovic J, Cuttone G, et al. Chromosome aberrations, micronuclei, and activity of superoxide dismutases in human lymphocytes after irradiation in vitro. Cell Mol Life Sci 2000;57:842–850.
  • Izutani R, Asano S, Imano M, Kuroda D, Kato M, Ohyanagi H. Expression of manganese superoxide dismutase in esophageal and gastric cancers. J Gastroenterol 1998;33:816–822.
  • Ho JCM, Zheng S, Comhair SAA, Farver C, Erzurum SC. Differential expression of manganese superoxide dismutase and catalase in lung cancer. Cancer Res 2001;61:8578–8585.
  • Toh Y, Kuninaka S, Oshiro T. Overexpression of manganese superoxide dismutase mRNA may correlate with aggressiveness in gastric and colorectal adenocarcinomas. Int J Oncol 2000;17:107–112.
  • Kamarajugadda S, Cai Q, Chen H, Nayak S, Zhu J, He M, et al. Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis. Cell Death Dis 2013;4:e504.
  • Malafa M, Margenthaler J, Webb B, Neitzel L, Christophersen M. MnSOD expression is increased in metastatic gastric cancer. J Surg Res 2000;88:130–134.
  • Oberley LW, Buettner GR. Role of superoxide dismutase in cancer: a review. Cancer Res 1979;39:1141–1149.
  • Keele BB Jr, MnCord JM, Fridovich I. Superoxide dismutase from Escherichia coli B. A new manganese-containing enzyme. J Biol Chem 1970;245:6176–6181.
  • Misra HP, Fridovich I. Purification and properties of superoxide dismutase from a red alga, Porphyridium cruentum. J Biol Chem. 1977;252:6421–6423.
  • Ravindranath SD, Fridovich I. Isolation and characterisation of a manganese-containing superoxide dismutase from yeast. J Biol Chem. 1975;250:6170–6112.
  • Weisiger RA, Fridovich I. Mitochondrial Superoxide simutase. Site of synthesis and intramitochondrial localization. J Biol Chem. 1973;248:4793–4796.
  • Holley AK, Dhar SK, Xu Y, St. Clair DK. Manganese Superoxide dismutase: beyond life and death. Amino acids 2012;42:139–158.
  • Yon MJ, Baek I, Lee BJ, Yun YW, Nam SY. Dynamic expression of manganese superoxide dismutase during mouse embryonic organogenesis. Int J Dev Biol 2011;55:327–334.
  • Legge M, Sellens MH. Free radical scavengers ameliorate the 2-cell block in mouse embryo culture. Hum Reprod 1991;6:867–871.
  • Peluffo H, Acarin L, Faiz M, Castellano B, Gonzalez B. Cu/Zn superoxide dismutase expression in the postnatal rat brain following an excitotoxic injury. J Neuroinflammation 2005;2:12–24.
  • Minim A, Asayama K, Dobashi K, Suzuki K, Kawaoi A, Kato K. Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues. J Histochem Cytochem 1992;40:1705–1713.
  • Oberley TD, Oberley LW, Slattery AF, Lauchner LJ, Elwell JH. Immunohistochemical localization of antioxidant enzymes in adult Syrian Hamster tissues and during kidney development. Am J Pathol 1990;137:199–214.
  • Minim A, Asayama K, Uchida N, Dobashi K, Hayashire H, Kobayashi M, et al. Immunohistochemical localization of copper-zinc and manganese superoxide dismutases in human tissues. Yanashi Med J 1990;5:181–188.
  • Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 2001;7:175–189.
  • Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature 1981;292:154–156.
  • Kim J, Chu J, Shen X, Wang J, Orkin SH. An extended transcriptional network for pluripotency of embryonic stem cells. Cells 2008;132:1049–1061.
  • Wanet A, Arnould T, Renard P. Mitochondrial involvement in stemness and stem cell differentiation. Cellular bioenergetics in health and diseases: new perspectives in mitochondrial biology 2012;195–215. ISBN: 978-81-308-0487-3.
  • Siggins RW, Zhang P, Welsh NJ, LeCapetaine NJ, Nelson S. Stem cells, phenotypic inversion, and differentiation. Int J Clin Exp Med 2008;1:2–21.
  • Chung S, Arrell DK, Faustino RS, Terzic A, Dzeja PP. Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation. J Mol Cell Cardiol 2010;48:725–734.
  • Pereira SL, Graos M, Rodrigues AS, Anjo SI, Carvalho RA, Oliviera PJ, et al. Inhibition of mitochondrial complex III blocks neuronal differentiation and maintains embryonic stem cell pluripotency. PLoS ONE 2013;8:e82095.
  • Cho YM, Kwon S, Pak YK, Seol HW, Choi YM, Park do J, et al. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem Biophys Res Commun 2006;348:1472–1478.
  • Trouillas M, Saucourt C, Guillotin B, Gauthereau X, Ding L, Buchholz F, et al. Three LIF-dependent signatures and gene clusters with atypical expression profiles, identified by transcriptome studies in mouse ES cells and early derivatives. BMC Genom 2009;10:73–92.
  • Lin T, Chao C, Saito S, Mazur SJ, Murphy ME, Appella E, et al. p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 2005;7:165–171.
  • Riley T, Sontag E, Chen P, Levin A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008;9:402–412.
  • Boehme KA, Blattner C. Regulation of p53 – insights into a complex process. Crit Rev Biochem Mol Biol 2009;44:367–392.
  • Zhao T, Xu Y. p53 and Stem cells: new developments and new concerns. Trends Cell Biol 2010;20:170–175.
  • Hou Y, Ouyang X, Wan R, Cheng H, Mattson MP, Cheng A. Mitochondrial superoxide production negatively regulates neural progenitor proliferation and cerebral cortical development. Stem Cells 2012;30:2535–2547.
  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663–676.
  • Armstrong L, Tilgner K, Saretzki G, Atkinson SP, Stojkovic M, Moreno R, et al. Human induced pluripotent stem cell lines show stress defense mechanisms and mitochondrial regulation similar to those of human embryonic stem cells. Stem Cells 2010;28:661–673.
  • Esteban MA, Wang T, Qin B, Yang J, Qin D, Cai J, et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 2010;6:71–79.
  • Porada CD, Atala AJ, Almeida-Porada G. The hematopoietic system in the context of regenerative medicine. Methods 2015; pii: S1046–S2023: 30057–30058.
  • Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell 2010;7:380–390.
  • Martin FM, Xu X, von Löhneysen K, Gilmartin TJ, Friedman JS. SOD2 deficient erythroid cells up-regulate transferrin receptor and down-regulate mitochondrial biogenesis and metabolism. PLoS One 2011;6:e16894.
  • Yalcin S, Mungamuri SK, Marinkovic D, Vercherat C, Sarkar A, Grisotto M, et al. Foxo3 is essential for the regulation of ataxia telangiectasia mutated and oxidative stress-mediated homeostasis of hematopoietic stem cells. J Biol Chem 2008;283:25692–25705.
  • Liang R, Ghaffari S. Stem cells, redox signaling, and stem cell aging. Antioxid Redox Signal 2014;20:1902–1916.
  • Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 2004;431:997–1002.
  • Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 2006;12:446–451.
  • Chen C, Liu Y, Liu R, Ikenoue T, Guan KL, Liu Y, et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J Exp Med 2008;205:2397–2408.
  • Mohanty JG, Nagababu E, Friedman JS, Rifkind JM. SOD2 deficiency in hematopoietic cells in mice results in reduced red blood cell deformability and increased heme degradation. Exp Hematol 2013;41:316–321.
  • Punekar NS, Gokhale RS. Factors influencing the stability of heme and ferrochelatase: role of oxygen. Biotechnol Appl Biochem 1991;14:21–29.
  • Case AJ, Madsen JM, Motto DG, Meyerholz DK, Domann FE. Manganese superoxide dismutase depletion in murine hematopoietic stem cells perturbs iron homeostasis, globin switching, and epigenetic control in erythrocyte precursos cells. Free Radic Biol Med 2013;56:17–27.
  • Martin FM, Bydlon G, Friedman JS. SOD2-deficiency sideroblastic anemia and red blood cell oxidative stress. Antioxid Redox Signal 2006;8:1217–1225.
  • Friedman JS, Rebel VI, Derby R, Bell K, Huang TT, Kuypers FA, et al. Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant. J Exp Med 2001;193:925–934.
  • Epperly MW, Dixon T, Wang H, Schlesselman J, Franicola D, Greenberger JS. Modulation of radiation-induced life shortening by systemic intravenous MnSOD-plasmid liposome gene therapy. Radiat Res 2008;170:437–443.
  • Epperly MW, Sikora CA, DeFilippi SJ, Gretton JA, Zhan Q, Kufe DW, et al. Manganese superoxide dismutase (SOD2) inhibits radiation-induced apoptosis by stabilization of the mitochondrial membrane. Radiat Res 2002;157:568–577.
  • Johnke RM, Abernathy RS, Kovacs CJ, Evans MJ, Biggs LE, Daly BM, et al. Antioxidant enzyme activity in murine hematopoietic bone marrow following treatment with interleukin 1 alpha: influence of tumor. Anticancer Res 1997;17:2169–2174.
  • Eastgate J, Moreb J, Nick HS, Suzuki K, Taniguchi N, Zucali JR. A role for manganese superoxide dismutase in radioprotection of hematopoietic stem cells by interleukin-1. Blood 1993;81:639–646.
  • Liu JM, Auerbach AD, Anderson SM, Green SW, Young NS. A trial of recombinant human superoxide dismutase in patients with Fanconi anaemia. Br J Haematol 1993;85:406–408.
  • Dumontet C, Drai J, Thieblemont C, Hequet O, Espinouse D, Bouafia F, et al. The superoxide dismutase content in erythrocytes predicts short-term toxicity of high-dose cyclophosphamide. Br J Haematol 2001;112:405–409.
  • Epperly MW, Bernarding M, Gretton J, Jefferson M, Nie S, Greenberger JS. Overexpression of the transgene for manganese superoxide dismutase (MnSOD) in 32D cl 3 cells prevents apoptosis induction by TNF-alpha, IL-3 withdrawal, and ionizing radiation. Exp Hematol 2003;31:465–474.
  • Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 2004;116:639–648.
  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143–147.
  • Atashi F, Modarressi A, Pepper MS. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review. Stem Cells Dev 2015;24:1150–1163.
  • Rehman J. Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J Mol Med (Berl) 2010;88:981–986.
  • Zhang Y, Marsboom G, Toth PT, Rehman J. Mitochondrial respiration regulates adipogenic differentiation of human mesenchymal stem cells. PLoS One 2013;8:e77077.
  • Sah SK, Pask KH, Yun CO, Kang KS, Kim TY. Effects of human mesenhymal stem cells transduced with superoxide dismutase on imiquimod-induced psoriasis-like skin inflammation in mice. Antioxid Redox Signal 2015;24:233–248.
  • Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 2008;26:960–968.
  • Jeong SG, Cho GW. Trichostatin A modulates intracellular reactive oxygen species through SOD2 and FOXO1 in human bone marrow-mesenchymal stem cells. Cell Biochem Funct 2015;33:37–43.
  • Li Z, Wang F, Roy S, Sen CK, Guan J. Injectable, highly flexible, and thermosensitive hydrogels capable of delivering superoxide dismutase. Biomacromolecules 2009;10:3306–3316.
  • Liu TC, Ismail S, Brennan O, Hastings C, Duffy GP. Encapsulation of cardiac stem cells in superoxide dismutase-loaded alginate prevents doxorubicin-mediated toxicity. J Tissue Eng Regen Med 2013;7:302–311.
  • Bobis S, Jarocha D, Maika M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol 2006;44:215–230.
  • Sart S, Song L, Li Y. Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation. Oxid Med Cell Longev 2015;2015:105135–105149.
  • Yang C, Chen HX, Zhou Y, Liu MX, Wang Y, Wang JX, et al. Manganese superoxide dismutase gene therapy protects against irradiation-induced intestinal injury. Curr Gene Ther 2013;13:305–314.
  • Zhang Y, Zhang HM, Shi Y, Lustgarten M, Li Y, Qi W, et al. Loss of manganese superoxide dismutase leads to abnormal growth and signal transduction in mouse embryonic fibroblasts. Free Radic Biol Med 2010;49:1255–1262.
  • Wu J, Niu J, Li X, Wang X, Guo Z, Zhang F. TGF-β1 induces senescence of bone marrow mesenchymal stem cells via increase of mitochondrial ROS production. BMC Dev Biol 2014;14:21–29.
  • Pietilä M, Palomäki S, Lehtonen S, Ritamo I, Valmu L, Nystedt J, et al. Mitochondrial function and energy metabolism in umbilical cord blood- and bone marrow-derived mesenchymal stem cells. Stem Cells Dev 2012;21:575–588.
  • Gan J, Meng F, Zhou X, Li C, He Y, Zeng X, et al. Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells. Cytotherapy 2015;17:403–417.
  • Dey R, Kemp K, Gray E, Rice C, Scolding N, Wilkins A. Human mesenchymal stem cells increase anti-oxidant defences in cells derived from patients with Friedreich’s ataxia. Cerebellum 2012;11:861–871.
  • Mateos J, De la Fuente A, Lesende-Rodriguez I, Fernández-Pernas P, Arufe MC, Blanco FJ. Lamin A deregulation in human mesenchymal stem cells promotes an impairment in their chondrogenic potential and imbalance in their response to oxidative stress. Stem Cell Res 2013;11:1137–1148.
  • Casaneuva E, Viteri FE (2003) Iron and oxidative stress in pregnancy. J Nutr 2003;133:1700S–1708S.
  • Liu SH, Huang JP, Lee RK, Huang MC, Wu YH, Chen CY, et al. Paracrine factors from human placental multipotent mesenchymal stromal cells protect endothelium from oxidative injury via STAT3 and manganese superoxide dismutase activation. Biol Reprod 2010;82:905–913.
  • Park CM, Kim MJ, Kim SM, Park JH, Kim ZH, Choi YS. Umbilical cord mesenchymal stem cell-conditioned media prevent muscle atrophy by suppressing muscle atrophy-related proteins and ROS generation. In Vitro Cell Dev Biol Anim 2016;52:68–76.
  • Harvey MB, Arcellana-Panlilio MY, Zhangs X, Schultz GA, Watson AJ. Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow embryos and primary bovine oviduct cultures employed for embryo coculture. Biol Reprod 1995;53:532–540.
  • Nozic-Grayck E, Dieterle CS, Piantadosi CA, Oury T. Extracellular superoxide dismutase secretion and activity during development. Pediatr Res 1999;45:44A–44A.
  • Oelze M, Kröller-Schön S, Steven S, Lubos E, Doppler C, Hausding M, et al. Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. Hypertension 2014;63:390–396.
  • Kamerbeek NM, van Zwieten R, de Boer M, Morren G, Vuil H, Bannink N, et al. Molecular basis of glutathione reductase deficiency in human blood cells. Blood 2007;109:3560–3566.

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