DOI QR코드

DOI QR Code

Peroxiredoxin I participates in the protection of reactive oxygen species-mediated cellular senescence

  • Park, Young-Ho ;
  • Kim, Hyun-Sun ;
  • Lee, Jong-Hee ;
  • Cho, Seon-A ;
  • Kim, Jin-Man ;
  • Oh, Goo Taeg ;
  • Kang, Sang Won ;
  • Kim, Sun-Uk ;
  • Yu, Dae-Yeul
  • Received : 2017.07.07
  • Accepted : 2017.09.12
  • Published : 2017.10.31

Abstract

Peroxiredoxin I (Prx I) plays an important role as a reactive oxygen species (ROS) scavenger in protecting and maintaining cellular homeostasis; however, the underlying mechanisms are not well understood. Here, we identified a critical role of Prx I in protecting cells against ROS-mediated cellular senescence by suppression of $p16^{INK4a}$ expression. Compared to wild-type mouse embryonic fibroblasts (WT-MEFs), Prx $I^{-/-}$ MEFs exhibited senescence-associated phenotypes. Moreover, the aged Prx $I^{-/-}$ mice showed an increased number of cells with senescence associated-${\beta}$-galactosidase (SA-${\beta}$-gal) activity in a variety of tissues. Increased ROS levels and SA-${\beta}$-gal activity, and reduction of chemical antioxidant in Prx $I^{-/-}$ MEF further supported an essential role of Prx I peroxidase activity in cellular senescence that is mediated by oxidative stress. The up-regulation of $p16^{INK4a}$ expression in Prx $I^{-/-}$ and suppression by overexpression of Prx I indicate that Prx I possibly modulate cellular senescence through $ROS/p16^{INK4a}$ pathway.

Keywords

Antioxidant enzyme;Cellular senescence;Oxidative stress;$p16^{INK4a}$;Peroxiredoxin

References

  1. Schmitt CA, Fridman JS, Yang M et al (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109, 335-346 https://doi.org/10.1016/S0092-8674(02)00734-1
  2. Sharpless NE and DePinho RA (2002) p53: good cop/bad cop. Cell 110, 9-12 https://doi.org/10.1016/S0092-8674(02)00818-8
  3. Moiseeva O, Bourdeau V, Roux A, Deschenes-Simard X and Ferbeyre G (2009) Mitochondrial dysfunction contributes to oncogene-induced senescence. Mol Cell Biol 29, 4495-4507 https://doi.org/10.1128/MCB.01868-08
  4. Barascu A, Le Chalony C, Pennarun G et al (2012) Oxidative stress induces an ATM-independent senescence pathway through p38 MAPK-mediated lamin B1 accumulation. EMBO J 31, 1080-1094 https://doi.org/10.1038/emboj.2011.492
  5. Frippiat C, Chen QM, Zdanov S, Magalhaes JP, Remacle J and Toussaint O (2001) Subcytotoxic H2O2 stress triggers a release of transforming growth factor-beta 1, which induces biomarkers of cellular senescence of human diploid fibroblasts. J Biol Chem 276, 2531-2537 https://doi.org/10.1074/jbc.M006809200
  6. Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S and Campisi J (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5, 741-747 https://doi.org/10.1038/ncb1024
  7. Smirnov A, Panatta E, Lena A et al (2016) FOXM1 regulates proliferation, senescence and oxidative stress in keratinocytes and cancer cells. Aging (Albany NY) 8, 1384-1397
  8. Labunskyy VM and Gladyshev VN (2013) Role of reactive oxygen species-mediated signaling in aging. Antioxid Redox Signal 19, 1362-1372 https://doi.org/10.1089/ars.2012.4891
  9. Ben-Porath I and Weinberg RA (2005) The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37, 961-976 https://doi.org/10.1016/j.biocel.2004.10.013
  10. Kim TR, Lee HM, Lee SY et al (2010) SM22alpha-induced activation of p16INK4a/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of gamma-radiation and doxorubicin in HepG2 cells. Biochem Biophys Res Commun 400, 100-105 https://doi.org/10.1016/j.bbrc.2010.08.018
  11. Ishii T, Yamada M, Sato H et al (1993) Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein. J Biol Chem 268, 18633-18636
  12. Park YH, Kim SU, Kwon TH et al (2016) Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway. Oncogene 35, 3503-3513 https://doi.org/10.1038/onc.2015.411
  13. Przedborski S (2007) Peroxiredoxin-2 links Cdk5 to neurodegeneration. Nat Med 13, 907-909 https://doi.org/10.1038/nm0807-907
  14. Yang HY and Lee TH (2015) Antioxidant enzymes as redox-based biomarkers: a brief review. BMB Rep 48, 200-208 https://doi.org/10.5483/BMBRep.2015.48.4.274
  15. Han YH, Kim HS, Kim JM, Kim SK, Yu DY and Moon EY (2005) Inhibitory role of peroxiredoxin II (Prx II) on cellular senescence. FEBS Lett 579, 4897-4902 https://doi.org/10.1016/j.febslet.2005.07.049
  16. Immenschuh S and Baumgart-Vogt E (2005) Peroxiredoxins, oxidative stress, and cell proliferation. Antioxid Redox Signal 7, 768-777 https://doi.org/10.1089/ars.2005.7.768
  17. Parmigiani RB, Xu WS, Venta-Perez G et al (2008) HDAC6 is a specific deacetylase of peroxiredoxins and is involved in redox regulation. Proc Natl Acad Sci U S A 105, 9633-9638 https://doi.org/10.1073/pnas.0803749105
  18. Kuilman T, Michaloglou C, Mooi WJ and Peeper DS (2010) The essence of senescence. Genes Dev 24, 2463-2479 https://doi.org/10.1101/gad.1971610
  19. Chen J, Huang X, Halicka D et al (2006) Contribution of p16INK4a and p21CIP1 pathways to induction of premature senescence of human endothelial cells: permissive role of p53. Am J Physiol Heart Circ Physiol 290, H1575-1586 https://doi.org/10.1152/ajpheart.00364.2005
  20. Blander G, de Oliveira RM, Conboy CM, Haigis M and Guarente L (2003) Superoxide dismutase 1 knock-down induces senescence in human fibroblasts. J Biol Chem 278, 38966-38969 https://doi.org/10.1074/jbc.M307146200
  21. de Haan JB, Bladier C, Lotfi-Miri M et al (2004) Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death. Free Radic Biol Med 36, 53-64
  22. Volonte D and Galbiati F (2009) Inhibition of thioredoxin reductase 1 by caveolin 1 promotes stress-induced premature senescence. EMBO Rep 10, 1334-1340 https://doi.org/10.1038/embor.2009.215
  23. Han YH, Kwon JH, Yu DY and Moon EY (2006) Inhibitory effect of peroxiredoxin II (Prx II) on Ras-ERK-NFkappaB pathway in mouse embryonic fibroblast (MEF) senescence. Free Radic Res 40, 1182-1189 https://doi.org/10.1080/10715760600868552
  24. Egler RA, Fernandes E, Rothermund K et al (2005) Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1. Oncogene 24, 8038-8050 https://doi.org/10.1038/sj.onc.1208821
  25. Yang DG, Liu L and Zheng XY (2008) Cyclin-dependent kinase inhibitor p16(INK4a) and telomerase may comodulate endothelial progenitor cells senescence. Ageing Res Rev 7, 137-146 https://doi.org/10.1016/j.arr.2008.02.001
  26. Turner-Ivey B, Manevich Y, Schulte J et al (2013) Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer. Oncogene 32, 5302-5314 https://doi.org/10.1038/onc.2012.624
  27. Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513-522 https://doi.org/10.1016/j.cell.2005.02.003
  28. Ko A, Han SY and Song J (2016) Dynamics of ARF regulation that control senescence and cancer. BMB Rep 49, 598-606 https://doi.org/10.5483/BMBRep.2016.49.11.120
  29. Krtolica A, Parrinello S, Lockett S, Desprez PY and Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci U S A 98, 12072-12077 https://doi.org/10.1073/pnas.211053698
  30. Lawrenson K, Grun B, Benjamin E, Jacobs IJ, Dafou D and Gayther SA (2010) Senescent fibroblasts promote neoplastic transformation of partially transformed ovarian epithelial cells in a three-dimensional model of early stage ovarian cancer. Neoplasia 12, 317-325 https://doi.org/10.1593/neo.91948
  31. Romagosa C, Simonetti S, Lopez-Vicente L et al (2011) p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors. Oncogene 30, 2087-2097 https://doi.org/10.1038/onc.2010.614
  32. Collado M and Serrano M (2010) Senescence in tumours: evidence from mice and humans. Nat Rev Cancer 10, 51-57 https://doi.org/10.1038/nrc2772
  33. Gorgoulis VG and Halazonetis TD (2010) Oncogeneinduced senescence: the bright and dark side of the response. Curr Opin Cell Biol 22, 816-827 https://doi.org/10.1016/j.ceb.2010.07.013
  34. Park YH, Kim SU, Lee BK et al (2013) Prx I suppresses K-ras-driven lung tumorigenesis by opposing redox-sensitive ERK/cyclin D1 pathway. Antioxid Redox Signal 19, 482-496 https://doi.org/10.1089/ars.2011.4421
  35. Cao J, Schulte J, Knight A et al (2009) Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO J 28, 1505-1517 https://doi.org/10.1038/emboj.2009.101
  36. Zhu J, Grace M, Casale J et al (1999) Characterization of replication-competent adenovirus isolates from large-scale production of a recombinant adenoviral vector. Hum Gene Ther 10, 113-121 https://doi.org/10.1089/10430349950019246
  37. Chiche JD, Schlutsmeyer SM, Bloch DB et al (1998) Adenovirus-mediated gene transfer of cGMP-dependent protein kinase increases the sensitivity of cultured vascular smooth muscle cells to the antiproliferative and pro-apoptotic effects of nitric oxide/cGMP. J Biol Chem 273, 34263-34271 https://doi.org/10.1074/jbc.273.51.34263

Cited by

  1. Targeting peroxiredoxin 1 impairs growth of breast cancer cells and potently sensitises these cells to prooxidant agents vol.119, pp.7, 2018, https://doi.org/10.1038/s41416-018-0263-y

Acknowledgement

Supported by : NST (National Research Council of Science & Technology), KRIBB, NRF