Volume 12, Issue 3 (Autumn 2015)                   Sci J Iran Blood Transfus Organ 2015, 12(3): 255-265 | Back to browse issues page

XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Mehrabi Habibabadi H, Amiri F, Moslemi E, Habibi Roudkenar M, Jalili M. Overexpression of Nrf2 in umbilical cord-derived mesenchymal stem cells upregulating cytoprotective genes, TXNRD1 and GCLC. Sci J Iran Blood Transfus Organ 2015; 12 (3) :255-265
URL: http://bloodjournal.ir/article-1-932-en.html
Full-Text [PDF 426 kb]   (3286 Downloads)     |   Abstract (HTML)  (5848 Views)
Full-Text:   (3179 Views)
    References :  
  1. Romanov YA, Darevskaya AN, Merzlikina NV, Buravkova LB. Mesenchymal stem cells from human bone marrow and adipose tissue: isolation, characterization, and differentiation potentialities. Bull Exp Biol Med 2005; 140(1): 138-43.
  2. Barry FP, Murphy JM. Mesenchymal stem cells: clinical application and biological characterization. Int J Biochem Cell Biol 2004; 36(4): 568-84.
  3. Schwartz L, Maitournam H, Stolz JM, Ho Ba Tho MC, Halphen B. Growth and cellular differentiation: a physicobiochemical conundrum? The example of the hand. Med Hypotheses 2003; 61(1): 45-51.
  4. Armesilla-Diaz A, Elvira G, Silva A. p53 regulates the proliferation differentiation and spontaneous transformation of mesenchymal stem cells. Exp Cell Res 2009; 315(20): 3598-610.
  5. Zhang W, Su X, Gao Y, Sun B, Yu Y, Wang X, et al. Berberine protects mesenchymal stem cells against hypoxia-induced apoptosis. Biol Pharm Bull 2009; 32(8): 1335-42.
  6. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109(12): 1543-9.
  7. Iwase T, Nagaya N, Fujii T, Itoh T, Murakami S, Matsumoto T, et al. Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia. Cardiovasc Res 2005; 66(3): 543-51.
  8. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002; 105(1): 93-8.
  9. Haider HK and Ashraf M. Strategies to promote donor cell survival: Combining preconditioning approach with stem cell transplantation. J Mol Cell Cardiol  2008; 45(4): 554-66.
  10. Yates MS, Tran QT, Dolan PM, Osburn WO, Shin S, McCulloch CC, et al. Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis   2009; 30(6): 1024-31.
  11. Lee  JM,  Calkins  MJ,  Chan  K,Kan YW, Johnson JA. Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in
 
 
 
 
 
primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 2003; 278(14): 12029-38.
  1. Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, et al. Activation of Nrf2- antioxidant signaling attenuates NFkappaB inflammatory response and elicits apoptosis. Biochem Pharmacol  2008; 76(11): 1485-9.
  2. Reisman SA, Yeager RL, Yamamoto M, Klaassen CD. Increased Nrf2 activation in livers from keap1- knockdown mice increases expression of cytoprotective genes that detoxify electrophiles more than those that detoxify reactive oxygen species. Toxicol Sci  2009; 108(1): 35-47.
  3. Jin W, Wang H, Ji Y, Zhu L, Yan W, Qiao L, et al. Genetic ablation of Nrf2 enhances susceptibility to acute lung injury after traumatic brain injury in mice. Exp Biol Med  2009; 234(2): 181-9.
  4. Lee J-M and Johnson JA. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 2004; 37(2): 139-43.
  5. Osburn WO, Wakabayashi N, Misra V, Nilles T, Biswal S, Trush MA, et al. Nrf2 regulates an adaptive response protecting against oxidative damage following diquat-mediated formation of superoxide anion. Arch Biochem Biophys 2006; 454(1): 7-15.
  6. Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N, et al. Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res 2009; 15(10): 3423-32.
  7. Lee JM, Li J, Johnson DA, Stein TD, Kraft AD, Calkins MJ, et al. Nrf2, a multi-organ protector? FASEB J 2005; 19(9): 1061-6.
  8. Eguchi-Ishimae M, Eguchi M, Ishii E, Knight D, Sadakane Y, Isoyama K, et al. The association of a distinctive allele of NAD(P)H: quinone oxidoreductase With Pediatric Acute Lymphoblastic Leukemias with MLL   fusion   genesin   Japan.   Haematologica   2005;
90(11): 1511-5.
  1. Fagerholm  R,  Hofstetter  B, Tommiska J, Aaltonen K, Vrtel R, Syrjäkoski K, et al. NAD(P)H: quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer. Nat Gene 2008; 40(7): 844-53.
  2. Katori M, Buelow R, Ke  B, Ma  J, Coito  AJ, Lyer S, et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway. Transplantation 2002; 73(2): 287-92.
  3. Ke B, Buelow R, Shen XD, Melinek J, Amersi F, Gao F, et al. Heme oxygenase 1 gene transfer prevents CD95/Fas ligand-mediated apoptosis and improves liver allograft survival via carbon monoxide signaling pathway. Hum Gene Ther 2002; 13(10): 1189-99.
  4. DeBruyne LA, Magee JC, Buelow R, Bromberg JS. Gene transfer of immunomodulatory peptides correlation with heme oxygenase-1 induction and enhanced allograft survival. Transplantation 2000; 69(1): 120-8.
  5. Papp LV, Lu J, Holmgren A. From selenium to selenoproteins: synthesis, identy, and their role in human health. Antioxid Redox Signal 2007; 9(7): 775-806.
  6. Gipp JJ, Chang C, Mulcahy RT. Cloning and nucleotide sequence of a full-length cDNA for human liver gamma-glutamylcysteine synthetase. Biochem Biophys Res Commun 1992; 185(1): 29-35.
  7. Mohammadzadeh M, Halabian R, Gharehbaghian A, Amirizadeh N, Jahanian-Najafabadi A, Roushandeh AM, et al. Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity. Cell Stress Chap 2012; 17(5): 553-65.
  8. Levonen AL, Inkala M, Heikura T, Jauhiainen S, Jyrkkanen HK, Kansanen E, et al. Nrf2 gene transfer induces antioxidant enzymes and suppresses smooth muscle cell growth in vitro and reduces oxidative stress in rabbit aorta in vivo. Arter Thromb Vas Biol  2007; 27(4): 741-47.
  9. Cao TT, Ma L, Kandpal G, Warren L, Hess JF, Seabrook GR. Increased nuclear factor-erythroid 2 p45-related factor 2 activity protects SH-SY5Y cells against oxidative damage. J Neurochem 2005; 95(2): 406-17.
  10. Amiri F, Halabian R, Salimian M, Shokrgozar MA, Soleimani M, Jahanian-Najafabadi A, et al. Induction of multipotency in umbilical cord-derived mesenchymal stem cells cultivated under suspension conditions. Cell Stress Chaperones 2014; 19(5): 657-66.
  11. Zhang J, Chen G, Wang Y, Zhao J, Duan H, Liao L, et al. Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Whartons Jelly mesenchymal stem cells after myocardial infarction. Chin Med J 2012; 125(19): 3472-8.
  12. Li W,Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, et al. Bcl-2 Engineered MSCs Inhibited Apoptosis and Improved Heart Function. Stem Cells 
    2007; 25(8): 2118-27.
  13. Zeng B, Lin G, Ren X, Zhang Y, Chen H. Over-expression of HO-1 on mesenchymal stem cell promotes angiogenesis and improves myocardial function in infracted myocardium. J Biomed Sci  2010; 17(1): 80-91.
  14. Venugopal P, Balasubramanina S, Majumdar AS, Ta m. Isolation, characterization, and gene expression analysis of Whartons Jelly-derived mesenchymal stem cell under xenofree culture conditions. Stem Cells Clon Adv App  2011; 4(1): 39-50.
  15. Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK, et al. Human Whartons Jelly stem cells have uniqe transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev Rep 2011; 7(1): 1-16.
  16. Troyer DL, Weiss ML. Concise review: Whartons Jelly-derived cells are a primitive stromal cell population. Stem Cells 2008; 26(3): 591-9.
  17. Bloom MV, Freyer GA, Micklos DA. Laboratory DNA Science. California: Benjamin Cummings; 1996. p. 298-320.
  18. Phillips AJ. The challenge of gene therapy and DNA delivery. J Pharm Pharmacol 2001; 53(9): 1169-74.
  19. Hoelters J, Ciccarella M, Drechsel M, Geissler C, Gülkan H, Böcker W, et al. Nonviral genetic modification mediates effective transgene expression and functional RNA interference in human mesenchymal stem cells. J Gene Med 2005; 7(6): 718-28.
  20. Reiser J, Zhang XY, Hemenway CS, Mondal D,  Pradhan L, La Russa VF. Potential of mesenchymal stem cells in gene therapy approaches for inherited and acquired diseases.  Expert Opin Biol Ther 2005; 5(12): 1571-84.
  21. Peister A, Mellad JA, Wang M, Tucker HA, Prockop DJ. Stable transfection of MSCs by electroporation. Gene Ther 2004; 11(2): 224-8.
  22. Keum YS, Owuor ED, Kim BR, Hu R, Kong AN. Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC). Pharm Res 2003; 20(9): 1351-6.
  23. Venugopal R, Jaiswal AK. Nrf1 and Nrf2 positively and C-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD (P) H: quinone oxidoreductase1 gene. Proc Natl Acad Sci  1995; 93(25): 14960-69.
  24. Sun XH, Erb A, Murphy TH. Coordinate regulation of glutathione metabolism in astrocytes by Nrf2. Biochem Biophys Res Commun  2005; 326(2): 371-7.
 
 
 
 
 
 
 


 
Original  Article
 

 
 
 
Sci J Iran Blood Transfus Organ 2015; 12(3): 255-265
 
Overexpression of Nrf2 in umbilical cord-derived
mesenchymal stem cells upregulating cytoprotective
genes, TXNRD1 and GCLC
 
 
Mehrabi Habibabadi H.1, Amiri F.2, Moslemi E.1, Habibi Roudkenar M.2, Jalili M.A.2
 
 
 
1Islmaic Azad University of East Tehran Branch, Tehran, Iran
2Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
 
 
Abstract
Background and Objectives
Due to the unique criteria, mesenchymal stem cells (MSCs) are the ideal cells for cell therapy and gene therapy. However, the low survival of MSCs after transplantation has limited their application. This study aimed to evaluate the expression of cytoprotective genes including NQO1, TXNRD1, HO-1, GCLC following the overexpression of Nrf2 in MSCs.
 
Materials and Methods
In this experimental study, umbilical cord-derived MSCs were cultured and recombinant vectors containing Nrf2 and empty vectors were transfected into MSCs using FuGENE HD. After exposure of the cells to stress, RNA extraction and cDNA generation were performed. Using Primer3 software, specific primers were designed for Nrf2, NQO1، TXNRD1، HO-1 and GCLC genes and the expression of these mentioned genes was evaluated by RT-PCR. The results were quantified and analyzed statistically utilizing Image J software and ANOVA.
Results
The expression of Nrf2 was up-regulated in MSCs after transfection (p< 0.01). Overexpression of TXNRD1 and GCLC was observed in transfected cells (p <0.05 and p <0.01); however, the expression of NQO1 and HO-1 did not change in the transfected group in comparison to the control (p > 0.05).
 
Conclusions
Overexpression of Nrf2 resulted in the overexpression of TXNRD1 and GCLC in MSCs and might be explained by the fact that a part of the known Nrf2 cytoprotective mechanisms is controlled by the expression of these genes.
 
Key words: Mesenchymal Stem Cells, NRF2 protein٬ human, TXNRD1 protein٬ human
 
 
 
 
Received: 20 Jan 2015
Accepted:  6 Jun 2015
 
 
 

Correspondence: Jalili M.A., PhD of Medicinal Chemistry. Assistant Professor of Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine.
P.O.Box: 14665-1157, Tehran, Iran. Tel: (+9821) 82052155; Fax: (+9821) 88601599
E-mail: m.jalili@ibto.ir
Type of Study: Research | Subject: Stem cells
Published: 2015/09/2

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 CC BY-NC 4.0 | Scientific Journal of Iran Blood Transfus Organ

Designed & Developed by : Yektaweb