Levels of DNA damage are unaltered in mice overexpressing human catalase in nuclei
Abstract
Two types of transgenic mice were generated to evaluate the role of hydrogen peroxide in the formation of nuclear DNA damage. One set of lines overexpresses wild-type human catalase cDNA, which is localized to peroxisomes. The other set overexpresses a human catalase construct that is targeted to the nucleus. Expression of the wild-type human catalase transgene was found in liver, kidney, skeletal muscle, heart, spleen, and brain with muscle and heart exhibiting the highest levels. Animals containing the nuclear-targeted construct had a similar pattern of expression with the highest levels in muscle and heart, but with lower levels in liver and spleen. In these animals, immunofluorescence detected catalase present in the nuclei of kidney, muscle, heart, and brain. Both types of transgenic animals had significant increases of catalase activities compared to littermate controls in most tissues examined. Despite enhanced activities of catalase, and its presence in the nucleus, there were no changes in levels of 8OHdG, a marker of oxidative damage to DNA. Nor were there differences in mutant frequencies at a Lac Z reporter transgene. This result suggests that in vivo levels of H(2)O(2) may not generate 8OHdG or other types of DNA damage. Alternatively, antioxidant defenses may be optimized such that additional catalase is unable to further protect nuclear DNA against oxidative damage.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
When human catalase is localized to peroxisomes or targeted to the nucleus in mice, no detectable reduction in mtDNA damage or significant extension of lifespan are observed.
“Interestingly, when human catalase is localized to peroxisomes or targeted to the nucleus in mice, no detectable reduction in mtDNA damage or significant extension of lifespan are observed (Schriner and Linford, 2006; Schriner et al., 2000).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Schriner et al., 2000
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178 · see citing works
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567 · see citing works
Efficient selection for high-expression transfectants with a novel eukaryotic vector
Niwa, H., Yamamura, K., & Miyazaki, J. (1991) · Gene · doi:10.1016/0378-1119(91)90434-d · Cited by 5,135 · see citing works
Free Radicals in Biology and Medicine
Land, E. J. (1990) · International Journal of Radiation Biology · doi:10.1080/09553009014552071 · Cited by 4,871 · see citing works
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879 · see citing works
Prooxidant States and Tumor Promotion
Cerutti, P. (1985) · Science · doi:10.1126/science.2981433 · Cited by 2,513 · see citing works
Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG
Shibutani, S., Takeshita, M., & Grollman, A. P. (1991) · Nature · doi:10.1038/349431a0 · Cited by 2,224 · see citing works
8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G-T and A-C substitutions.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., & Loeb, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48474-8 · Cited by 1,844 · see citing works
Oxygen poisoning and x-irradiation: a mechanism in common
Gerschman, R., Gilbert, D. L., Nye, S. W., Dwyer, P., & Fenn, W. O. (1954) · Science · doi:10.1126/science.119.3097.623 · Cited by 961 · see citing works
Helbock, H. J., Beckman, K. B., Shigenaga, M. K., Walter, P. B., Woodall, A., Yeo, H. C. H., & Ames, B. N. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.288 · Cited by 688 · see citing works
Damage to the Bases in DNA Induced by Hydrogen Peroxide and Ferric Ion Chelates
Aruoma, O. I., Halliwell, B. B., Gajewski, E., & Dizdaroğlu, M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47091-9 · Cited by 327 · see citing works
Technologies for Detection of DNA Damage and Mutations
Pfeifer, G. P. (1996) · Springer eBooks · doi:10.1007/978-1-4899-0301-3 · Cited by 262 · see citing works
Rapid accumulation of genome rearrangements in liver but not in brain of old mice
Dollé, M. E. T., Giese, H., Hopkins, C. L., Martus, H., Hausdorff, J. M., & Vijg, J. (1997) · Nature Genetics · doi:10.1038/ng1297-431 · Cited by 248 · see citing works
Joenje, H. (1989) · Mutation Research/DNAging · doi:10.1016/0921-8734(89)90001-5 · Cited by 197 · see citing works
Wang, L., Hirayasu, K., Ishizawa, M., & Kobayashi, Y. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.9.1774 · Cited by 186 · see citing works
Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Henle, E. S., Luo, Y., Gassmann, W., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21177 · Cited by 175 · see citing works
Oxidative Damage to DNA Constituents by Iron-mediated Fenton Reactions
Luo, Y., Henle, E. S., & Linn, S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.35.21167 · Cited by 159 · see citing works
Catalase: an old enzyme with a new role?
Percy, M. E. (1984) · Canadian Journal of Biochemistry and Cell Biology · doi:10.1139/o84-129 · Cited by 91 · see citing works
Immunolocalization of antioxidant enzymes in adult hamster kidney
Muse, K. E., Oberley, T. D., Sempf, J. M., & Oberley, L. W. (1994) · The Histochemical Journal · doi:10.1007/bf00158205 · Cited by 90 · see citing works
Bacteriophage Lambda and Plasmid lacZ Transgenic Mice for Studying Mutations in Vivo
Vijg, J., & Douglas, G. R. (1996) · Springer eBooks · doi:10.1007/978-1-4899-0301-3_29 · Cited by 71 · see citing works
Complete cDNA and 5′ Genomic Sequences and Multilevel Regulation of the Mouse Catalase Gene
Reimer, D. L., Bailley, J., & Singh, S. M. (1994) · Genomics · doi:10.1006/geno.1994.1273 · Cited by 68 · see citing works
Stogner, S. W., & Payne, D. K. (1992) · Annals of Pharmacotherapy · doi:10.1177/106002809202601214 · Cited by 41 · see citing works
Use of transgenic mouse models for studying somatic mutations in aging
Martus, H., Dollé, M. E. T., Gossen, J. A., Boerrigter, M. E. T. I., & Vijg, J. (1995) · Mutation Research/DNAging · doi:10.1016/0921-8734(95)00025-2 · Cited by 35 · see citing works
Wall, R. J., Hyman, P., Kerr, D., Pintado, B., & Wells, K. D. (1994) · Elsevier eBooks · doi:10.1016/c2009-0-02427-1 · Cited by 18 · see citing works
Yasmineh, W. G., Chung, M., & Caspers, J. I. (1992) · Clinical Biochemistry · doi:10.1016/0009-9120(92)80041-e · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724 · see citing works
Mitochondrial Energetics and Therapeutics
Wallace, D. C., Fan, W., & Procaccio, V. (2010) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092314 · Cited by 727 · see citing works
Mitochondrial DNA mutations in disease and aging
Wallace, D. C. (2010) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20586 · Cited by 622 · see citing works
Paradoxical Roles of Antioxidant Enzymes: Basic Mechanisms and Health Implications
Lei, X. G., Zhu, J., Cheng, W.-H., Bao, Y., Ho, Y.-S., Reddi, A. R., Holmgren, A., & Arnér, E. S. J. (2015) · Physiological Reviews · doi:10.1152/physrev.00010.2014 · Cited by 437 · see citing works
Is the Mitochondrial Free Radical Theory of Aging Intact?
Sanz, A., Pamplona, R., & Barja, G. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.582 · Cited by 240 · see citing works
Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management.
(2013) · Europe PMC (PubMed Central) · Cited by 209 · see citing works
The pathophysiology of mitochondrial disease as modeled in the mousePreprint
Wallace, D. C., & Fan, W. (2009) · Genes & Development · doi:10.1101/gad.1784909 · Cited by 201 · see citing works
DeBalsi, K. L., Hoff, K. E., & Copeland, W. C. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.006 · Cited by 180 · see citing works
Cells discover fire: Employing reactive oxygen species in developmentand consequences for aging
de Magalhães, J. P., & Church, G. M. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.09.002 · Cited by 109 · see citing works
Frequency and Pattern of Heteroplasmy in the Complete Human Mitochondrial Genome
Ramos, A., dos Santos, C. M. P., Mateiu, L. M., Gonzalez, M. D. M., Álvarez, L., Azevedo, L., Amorim, A., & Aluja, M. P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074636 · Cited by 90 · see citing works
Pereira, C. V., Nadanaciva, S., Oliveira, P. J., & Will, Y. (2012) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2012.645536 · Cited by 85 · see citing works
Catalase transgenic mice: characterization and sensitivity to oxidative stress
Chen, X., Liang, H., Remmen, H. V., Vijg, J., & Richardson, A. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.12.023 · Cited by 77 · see citing works
Removal of H2O2 and generation of superoxide radical: Role of cytochrome c and NADH
Velayutham, M., Hemann, C. F., & Zweier, J. L. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.007 · Cited by 69 · see citing works
Oxidative Damage and Aging: Spotlight on Mitochondria
Linford, N. J., Schriner, S. E., & Rabinovitch, P. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3163 · Cited by 67 · see citing works
Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations
de Magalhães, J. P. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2004.05.003 · Cited by 54 · see citing works
Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging
Hamilton, R. T. (2012) · Journal of Clinical & Experimental Pathology · doi:10.4172/2161-0681.s4-005 · Cited by 52 · see citing works
Redox homeostasis and age‐related deficits in neuromuscular integrity and function
Sakellariou, G. K., Lightfoot, A. P., Earl, K. E., Stofanko, M., & McDonagh, B. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12223 · Cited by 49 · see citing works
Mitochondrial diseases and the role of the yeast models
Rinaldi, T., Dallabona, C., Ferrero, I., Frontali, L., & Bolotin‐Fukuhara, M. (2010) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2010.00685.x · Cited by 47 · see citing works
Chen, X. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00161-6 · Cited by 47 · see citing works
Anisimov, V. N. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00262-7 · Cited by 41 · see citing works
Orthosiphon grandiflorum has a protective effect in a calcium oxalate stone forming rat model
Akanae, W., Tsujihata, M., Yoshioka, I., Nonomura, N., & Okuyama, Ä. (2010) · Urological Research · doi:10.1007/s00240-010-0265-6 · Cited by 35 · see citing works
Temporal Effects of Catalase Overexpression on Healing After Myocardial Infarction
Pendergrass, K. D., Varghese, S. T., Maiellaro-Rafferty, K., Brown, M. E., Taylor, W. R., & Davis, M. E. (2010) · Circulation Heart Failure · doi:10.1161/circheartfailure.110.957712 · Cited by 28 · see citing works
Aging and cancer in transgenic and mutant mice
Anisimov, V. N. (2003) · Frontiers in bioscience · doi:10.2741/1122 · Cited by 19 · see citing works
Role of mitochondrial DNA replication during differentiation of reprogrammed stem cells
Kelly, R. D., & John, J. C. S. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.103202rk · Cited by 18 · see citing works
An Objective Appraisal of the Free Radical Theory of Aging
Lustgarten, M. S., Müller, F. L., & Remmen, H. V. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-378638-8.00008-7 · Cited by 16 · see citing works
Cancer and aging: The molecular pathways
Bassi, P., & Sacco, E. (2009) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2009.07.013 · Cited by 15 · see citing works
Generation of Genetically Altered Mouse Models for Aging Studies
Treuting, P. M., Hopkins, H. C., Ware, C. A., Rabinovitch, P., & Ladiges, W. (2002) · Experimental and Molecular Pathology · doi:10.1006/exmp.2001.2405 · Cited by 13 · see citing works
Genetic Engineering of Mice to Test the Oxidative Damage Theory of Aging
Martin, G. M. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1323.005 · Cited by 12 · see citing works
Ortiz, J. G. M., Wallace, K., Leinisch, F., Kadiiska, M. B., Mason, R. P., & Kligerman, A. D. (2013) · Environmental and Molecular Mutagenesis · doi:10.1002/em.21780 · Cited by 9 · see citing works
Ghorbanihaghjo, A., Veisi, P., Argani, H., Shahsavari, M. A., Noroozianavval, M., Rashtchizadeh, N., Abbasi, M. M., Safa, J., & Babaei, H. (2008) · Clinical and Experimental Nephrology · doi:10.1007/s10157-007-0001-x · Cited by 5 · see citing works
(2014) · ASM Press eBooks · doi:10.1128/9781555816704.ch24 · Cited by 3 · see citing works
Exploring the Mechanism of Aging Using Rodent Models
Ikeno, Y., & Remmen, H. V. (2003) · Springer eBooks · doi:10.1007/978-94-017-0671-1_9
Nutritional Modulation of Aging: Effect of Caloric Restriction
Pahlavani, M. A., Hamilton, M. L., & Richardson, A. G. (2003) · Springer eBooks · doi:10.1007/978-94-017-0283-6_15
- Authors
- Schriner, S. E., Ogburn, C. E., Smith, A. C., Newcomb, T. G., Ladiges, W. C., Dollé, M. E. T., Vijg, J., Fukuchi, K.-I., & Martin, G. M.
- Affiliations
- University of Washington (US)
- The University of Texas at San Antonio (US)
- University of Alabama (US)
- Corresponding author
- Martin, George M
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 29
- Issue
- 7
- Pages
- 664-673
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2171522573
- Cited by
- 34
- References
- 27
- Citations by year
- 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 00057, P01AG001751, AG01751)
- National Institute of General Medical Sciences (GM07735, T32GM007735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- catalase, hydrogen peroxide, nuclear DNA damage, 8-oxoguanine, oxidative DNA damage, transgenic mice, antioxidant defense, peroxisomes, tissue-specific gene expression
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Animals, Brain, Catalase, Cell Nucleus, Crosses, Genetic, Deoxyguanosine, DNA Damage, Humans, Kidney, Mice, Inbred C57BL, Mice, Inbred Strains, Mice, Transgenic, Myocardium, Biomarkers, DNA, Complementary, Oxidative Stress, Muscle, Skeletal, Peroxisomes, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
