Skip to main content
Log in

Increased Catalase Activity in Mouse Cell Mutants Resistant to Paraquat

  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Paraquat is widely used as a generator of superoxide radicals in a cell. First it was shown to immediately induce premature senescence in normal human fibroblasts. To assess its defense mechanisms, we characterized three paraquat-resistant mutants from mouse FM3A cells, MPQR40-1 and MPQR40-3 isolated by a single-step selection after mutagenesis, and SPQR100-6 isolated spontaneously. All exhibited six to eight times more resistance to paraquat than the parental line. In cell—cell hybrids, their phenotypes were reccessive, co-dominant, or dominant, respectively. Biochemical characterization revealed that activity and mRNA level for catalase were increased in all of the mutants. In MPQR40-3 that showed the highest degree of paraquat resistance, total SOD activity and mRNA level for Cu/Zn—SOD were also increased. These results suggest that catalase plays a major role in paraquat resistance in mouse FM3A cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ayusawa D, Iwata K and Seno T (1981) Alteration of ribonucleotide reductase in aphidicolin-resistant mutants of mouse FM3A cells with associated resistance to arabinosyl-adenine and arabinosylcytosine. Somatic Cell Genet 7: 27–42

    Article  PubMed  Google Scholar 

  • Ayusawa D, Koyama H, Iwata K and Seno T (1980) Single-step selection of mouse FM3A cell mutants defective in thymidylate synthetase. Somatic Cell Genet 6: 261–270

    Article  PubMed  Google Scholar 

  • Beers RF and Sizer IW (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195: 133–140

    PubMed  Google Scholar 

  • Blair IA (2001) Lipid hydroperoxide-mediated DNA damage. Exp Gerontol 36: 1473–1481

    Article  PubMed  Google Scholar 

  • Bluher M, Kahn BB and Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299: 572–574

    Google Scholar 

  • Bradley MO and Dysart G (1985) DNA single-strand breaks, double-strand breaks and crosslinks in rat testicular germ cells: measurements of their formation and repair by alkaline and neutral filter elution. Cell Biol Toxicol 1: 181–195

    Article  PubMed  Google Scholar 

  • Chen Q and Ames BN (1994) Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc Natl Acad Sci USA 91: 4130–4134

    PubMed  Google Scholar 

  • Chen Q, Fischer A, Reagan JD, Yan LJ and Ames BN (1995) Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci USA 92: 4337–4341

    PubMed  Google Scholar 

  • Chomczynski P and Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159

    Article  PubMed  Google Scholar 

  • Croteau DL and Bohr VA (1997) Repair of oxidative damage to nuclear and mitochondrial DNA in mammalian cells. J Biol Chem 272: 25409–25412

    Article  PubMed  Google Scholar 

  • Cutler RG (1991) Human longevity and aging: possible role of reactive oxygen species. Ann NY Acad Sci 621: 1–28

    Google Scholar 

  • Dean RT, Fu S, Stocker R and Davies MJ (1997) Biochemistry and pathology of radical-mediated protein oxidation. Biochem J 324 (Pt 1): 1–18

    PubMed  Google Scholar 

  • Farrington JA, Ebert M, Land EJ and Fletcher K (1973) Bipyridylium quaternary salts and related compounds. V. Pulse radiolysis studies of the reaction of paraquat radical with oxygen. Implications for the mode of action of bipyridyl herbicides. Biochim Biophys Acta 314: 372–381

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Fukamatsu Y, Yabe N and Hasunuma K (2003) Arabidopsis NDK1 is a component of ROS signaling by interacting with three catalases. Plant Cell Physiol 44: 982–989

    Article  PubMed  Google Scholar 

  • Hassan HM and Fridovich I (1978) Superoxide radical and the oxygen enhancement of the toxicity of paraquat in Escherichia coli. J Biol Chem 253: 8143–8148

    PubMed  Google Scholar 

  • Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P and Le Bouc Y (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421: 182–187

    Article  PubMed  Google Scholar 

  • Honda S and Matsuo M (1983) Shortening of the in vitro lifespan of human diploid fibroblasts exposed to hyperbaric oxygen. Exp Gerontol 18: 339–345

    Article  PubMed  Google Scholar 

  • Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T and Goldschmidt-Clermont PJ (1997) Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 275: 1649–1652

    Article  PubMed  Google Scholar 

  • Ishii N, Takahashi K, Tomita S, Keino T, Honda S, Yoshino K and Suzuki K (1990) A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat Res 237: 165–171

    PubMed  Google Scholar 

  • Kelner MJ and Bagnell R (1990) Glutathione-dependent enzymes alone can produce paraquat resistance. Free Radic Biol Med 9: 149–153

    Article  PubMed  Google Scholar 

  • Krall J, Bagley AC, Mullenbach GT, Hallewell RA and Lynch RE (1988) Superoxide mediates the toxicity of paraquat for cultured mammalian cells. J Biol Chem 263: 1910–1914

    PubMed  Google Scholar 

  • Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA 90: 8905–8909

    PubMed  Google Scholar 

  • Lee TC, Lin FM, Ho IC, Liu TY, Wang TC, Chu YI and Chang HY (1990) Paraquat-resistant cell lines derived from Chinese hamster ovary cells. Cell Biol Int Rep 14: 235–246

    Article  PubMed  Google Scholar 

  • Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, Lanfrancone L and Pelicci PG (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402: 309–313

    Article  PubMed  Google Scholar 

  • Orr WC and Sohal RS (1992) The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster. Arch Biochem Biophys 297: 35–41

    Article  PubMed  Google Scholar 

  • Orr WC and Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263: 1128–1130

    PubMed  Google Scholar 

  • Sado K, Ayusawa D, Enomoto A, Suganuma T, Oshimura M, Sato K and Koyama H (2001) Identification of a mutated DNA ligase IV gene in the X-ray-hypersensitive mutant SX10 of mouse FM3A cells. J Biol Chem 276: 9742–9748

    Article  PubMed  Google Scholar 

  • Speranza MJ, Bagley AC and Lynch RE (1993) Cells enriched for catalase are sensitized to the toxicities of bleomycin, adriamycin, and paraquat. J Biol Chem 268: 19039–19043

    PubMed  Google Scholar 

  • Stadtman ER (1992) Protein oxidation and aging. Science 257: 1220–1224

    Google Scholar 

  • Suzuki T, Minagawa S, Michishita E, Ogino H, Fujii M, Mitsui Y and Ayusawa D (2001) Induction of senescence-associated genes by 5-bromodeoxyuridine in HeLa cells. Exp Gerontol 36: 465–474

    Article  PubMed  Google Scholar 

  • von Zglinicki T, Saretzki G, Docke W and Lotze C (1995) Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence? Exp Cell Res 220: 186–193

    Article  PubMed  Google Scholar 

  • Weidner MF, Sigurdsson ST and Hopkins PB (1990) Sequence preferences of DNA interstrand cross-linking agents: dG-to-dG cross-linking at 5'-CG by structurally simplified analogues of mitomycin C. Biochemistry 29: 9225–9233

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dai Ayusawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joguchi, A., Fujii, M. & Ayusawa, D. Increased Catalase Activity in Mouse Cell Mutants Resistant to Paraquat. Biogerontology 5, 193–200 (2004). https://doi.org/10.1023/B:BGEN.0000031157.12946.e3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:BGEN.0000031157.12946.e3

Navigation