Volume 7, Issue 2, December 2019, Page: 14-22
Menadione Induces DNA Damage and Superoxide Radical Level In HEK293 Cells
Alireza Ghodsi Senejani, Department of Biology and Environmental Science, University of New Haven, West Haven, USA
Joseph Matthew Magrino, Department of Biology and Environmental Science, University of New Haven, West Haven, USA
Amanda Marston, Department of Biology and Environmental Science, University of New Haven, West Haven, USA
Michelle Gregoire, Department of Biology and Environmental Science, University of New Haven, West Haven, USA
Khoa Dang Dinh, Department of Mathematics, University of New Haven, West Haven, USA
Received: Nov. 15, 2019;       Accepted: Dec. 2, 2019;       Published: Dec. 11, 2019
DOI: 10.11648/j.cb.20190702.11      View  472      Downloads  190
Abstract
Reactive oxygen species (ROS) can damage cellular components, including mitochondrial and genomic DNA. Oxidized DNA can transgress into lethal double stranded breaks if not adequately repaired. Clinical reports of the major neurodegenerative diseases have denoted the presence of oxidized genomic DNA with no clear understanding of their role in disease progression. To date, little is known on the neuronal vulnerability and repair kinetics of oxidative damage. Here, we studied how DNA repair kinetics contributes to reduce neuronal viability in oxidative stress conditions. To induce internal oxidative stress, we exposed neuronal-like HEK293 and fibroblast cells to 2-Methyl-1, 4-napthoquinone (Menadione). We found HEK293 cells have a reduced viability in response to induced oxidative stress compared to fibroblasts. Furthermore data obtained from COMET analysis show increased level of DNA breaks and regressed DNA repair kinetics in treated cells. Our results show that HEK293 cells have a regressed repair kinetics that allows for oxidative damage to transgress into lethal forms of DNA damage. Our findings indicate that oxidative stress can play a key role in neurodegenerative diseases and alleviation of their presence could increase neuronal survival.
Keywords
Reactive Oxygen Species (ROS), Menadione, Oxidative Stress, Superoxide Radical, Neurodegenerative Diseases
To cite this article
Alireza Ghodsi Senejani, Joseph Matthew Magrino, Amanda Marston, Michelle Gregoire, Khoa Dang Dinh, Menadione Induces DNA Damage and Superoxide Radical Level In HEK293 Cells, Cell Biology. Vol. 7, No. 2, 2019, pp. 14-22. doi: 10.11648/j.cb.20190702.11
Copyright
Copyright © 2019 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Mathers, C. D., et al., Causes of international increases in older age life expectancy. Lancet, 2015. 385 (9967): p. 540-8.
[2]
Brown, R. C., A. H. Lockwood, and B. R. Sonawane, Neurodegenerative diseases: an overview of environmental risk factors. Environ Health Perspect, 2005. 113 (9): p. 1250-6.
[3]
Hampel, H., et al., The future of Alzheimer's disease: the next 10 years. Prog Neurobiol, 2011. 95 (4): p. 718-28.
[4]
Mayeux, R., Epidemiology of neurodegeneration. Annu Rev Neurosci, 2003. 26: p. 81-104.
[5]
Przedborski, S., M. Vila, and V. Jackson-Lewis, Neurodegeneration: what is it and where are we? J Clin Invest, 2003. 111 (1): p. 3-10.
[6]
Cooke, M. S., et al., Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J, 2003. 17 (10): p. 1195-214.
[7]
Lin, M. T. and M. F. Beal, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006. 443 (7113): p. 787-95.
[8]
Ross, C. A. and M. A. Poirier, Protein aggregation and neurodegenerative disease. Nat Med, 2004. 10 Suppl: p. S10-7.
[9]
Shukla, V., S. K. Mishra, and H. C. Pant, Oxidative stress in neurodegeneration. Adv Pharmacol Sci, 2011. 2011: p. 572634.
[10]
Andersen, J. K., Oxidative stress in neurodegeneration: cause or consequence? Nat Med, 2004. 10 Suppl: p. S18-25.
[11]
Wang, H., et al., Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target? Mech Ageing Dev, 2017. 161 (Pt A): p. 163-176.
[12]
Chen, T. S., J. P. Richie, Jr., and C. A. Lang, The effect of aging on glutathione and cysteine levels in different regions of the mouse brain. Proc Soc Exp Biol Med, 1989. 190 (4): p. 399-402.
[13]
Sasaki, T., et al., Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain. Nucl Med Biol, 2001. 28 (1): p. 25-31.
[14]
Martin, L. J., DNA damage and repair: relevance to mechanisms of neurodegeneration. J Neuropathol Exp Neurol, 2008. 67 (5): p. 377-87.
[15]
Narciso, L., et al., The Response to Oxidative DNA Damage in Neurons: Mechanisms and Disease. Neural Plast, 2016. 2016: p. 3619274.
[16]
Gandhi, S. and A. Y. Abramov, Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev, 2012. 2012: p. 428010.
[17]
Halilovic, A., et al., Menadione-Induced DNA Damage Leads to Mitochondrial Dysfunction and Fragmentation During Rosette Formation in Fuchs Endothelial Corneal Dystrophy. Antioxid Redox Signal, 2016. 24 (18): p. 1072-83.
[18]
Iyanagi, T. and I. Yamazaki, One-electron-transfer reactions in biochemical systems. V. Difference in the mechanism of quinone reduction by the NADH dehydrogenase and the NAD (P) H dehydrogenase (DT-diaphorase). Biochim Biophys Acta, 1970. 216 (2): p. 282-94.
[19]
Thor, H., et al., The metabolism of menadione (2-methyl-1, 4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells. J Biol Chem, 1982. 257 (20): p. 12419-25.
[20]
Stepanenko, A. A. and V. V. Dmitrenko, HEK293 in cell biology and cancer research: phenotype, karyotype, tumorigenicity, and stress-induced genome-phenotype evolution. Gene, 2015. 569 (2): p. 182-90.
[21]
Shaw, G., et al., Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells. FASEB J, 2002. 16 (8): p. 869-71.
[22]
Thomas, P. and T. G. Smart, HEK293 cell line: a vehicle for the expression of recombinant proteins. J Pharmacol Toxicol Methods, 2005. 51 (3): p. 187-200.
[23]
Loor, G., et al., Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis. Free Radic Biol Med, 2010. 49 (12): p. 1925-36.
[24]
Oka, S., et al., Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs. EMBO J, 2008. 27 (2): p. 421-32.
[25]
Lorenzo, Y., et al., The comet assay, DNA damage, DNA repair and cytotoxicity: hedgehogs are not always dead. Mutagenesis, 2013. 28 (4): p. 427-32.
[26]
van Gent, D. C., J. H. Hoeijmakers, and R. Kanaar, Chromosomal stability and the DNA double-stranded break connection. Nat Rev Genet, 2001. 2 (3): p. 196-206.
[27]
Bradley-Whitman, M. A., et al., Nucleic acid oxidation: an early feature of Alzheimer's disease. J Neurochem, 2014. 128 (2): p. 294-304.
[28]
Keogh, M. J. and P. F. Chinnery, Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta, 2015. 1847 (11): p. 1401-11.
[29]
Nishiyama, T., et al., Cooperation of NAD (P) H: quinone oxidoreductase 1 and UDP-glucuronosyltransferases reduces menadione cytotoxicity in HEK293 cells. Biochem Biophys Res Commun, 2010. 394 (3): p. 459-63.
[30]
Parrinello, S., et al., Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol, 2003. 5 (8): p. 741-7.
[31]
Martins, E. A. and R. Meneghini, DNA damage and lethal effects of hydrogen peroxide and menadione in Chinese hamster cells: distinct mechanisms are involved. Free Radic Biol Med, 1990. 8 (5): p. 433-40.
[32]
Kashfi, K., Anti-inflammatory agents as cancer therapeutics. Adv Pharmacol, 2009. 57: p. 31-89.
[33]
Azzam, E. I., J. P. Jay-Gerin, and D. Pain, Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett, 2012. 327 (1-2): p. 48-60.
[34]
Hassan, G. S., Menadione. Profiles Drug Subst Excip Relat Methodol, 2013. 38: p. 227-313.
Browse journals by subject