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2018 | 27 | 3 |

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Influence of deltamethrin and cypermethrin on the expression of SUMO isoforms and UBC9

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Deltamethrin and cypermethrin are extensively used insecticides to which humans are widely exposed. The present study is designed to analyze the effects of these two pesticides on HePG2 cell lines and on differentiated 3T3-L1 and C2C12 cells with respect to the expression of small ubiquitinlike modifiers (SUMO) and SUMO-conjugating enzyme UBC9. Treatment of HePG2 cells with either deltamethrin or cypermethrin caused elevated mRNA levels of SUMO 2 and 3 as well as UBC9. This was associated with elevated nitric oxide and nitric oxide synthase mRNA levels and decreased NADPH levels. Differentiated 3T3-L1 cells treated with either deltamethrin or cypermethrin led to increased mRNA levels of inflammatory cytokines IL-Iβ and IL-6, indicating that these pesticides promote the inflammatory response. These observations are significant since previous studies reported that UBC9 and SUMO isoforms are upregulated in many types of cancers and hence the extensive use of these pesticides is a concern.

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  • Department of Biotechnology, BMS College of Engineering, Bengaluru 560019, India
  • Connexios Life Sciences Pvt Ltd, Bengaluru 560004, India
  • Department of Biotechnology, BMS College of Engineering, Bengaluru 560019, India
  • Department of Biotechnology, BMS College of Engineering, Bengaluru 560019, India


  • 1. HAY R.T. SUMO: A history of modification. Mol Cell 18, 1, 2005.
  • 2. JOHNSON E.S. Protein modification by SUMO, Annu. Rev. Biochem 73, 355, 2004.
  • 3. KIM K.I., BAEK S.H., CHUNG C.H. Versatile protein tag, SUMO: Its enzymology and biological function. J Cell Physiol 19, 257, 2002.
  • 4. LIANG Y.C., LEE C.C., YAO Y.L., LAI C.C., SCHMITZ M.L., YANG W.M. SUMO5, a Novel Poly-SUMO Isoform, Regulates PML Nuclear Bodies. Scientific Reports. 6, 26509, 2016.
  • 5. HICKEY C.M., WILSON N.R., HOCHSTRASSER M. Function and Regulation of SUMO proteases. NIH Public Access 13, 755, 2013.
  • 6. GALISSON F., MAHROUCHE L., COURCELLES M., BONNEIL E., MELOCHE S., CHELBI-ALIX M.K., THIBAULT P. A novel proteomics approach to identify SUMOylated proteins and their modification sites in human cells. Mol. Cell. Proteomics 10, M110.004796, 2011.
  • 7. SAITOH H., HINCHEY J. Functional heterogeneity of small ubiquitin-related protein modifiers SUMO-1 versus SUMO-2/3. J Biol Chem 275, 6252, 2000.
  • 8. MANZA L.L., CODREANU S.G., STAMER S.L., SMITH D.L., WELLS K.S., ROBERTS R.L., LIEBLER D.C. Global shifts in protein sumoylation in response to electrophile and oxidative stress. Chem. Res. Toxicol 17, 1706, 2004.
  • 9. TEMPÉ D., PIECHACZYK M., BOSSIS G. SUMO under stress. Biochem Soc Trans 36, 874, 2008.
  • 10. KIM H.J., YUN J., LEE J., HONG H., JEONG J., KIM E., BAE Y.S., LEE K.J. SUMO1 attenuates stress-induced ROS generation by inhibiting NADPH oxidase 2. Biochem. Biophys. Res. Commun 410, 555, 2011.
  • 11. BETTERMANN K., BENESCH M., WEIS S., HAYBAECK, J. SUMOylation in carcinogenesis. Cancer Lett 316, 113, 2012
  • 12. FLOTHO A., MELCHIOR F. SUMOYLATION: A Regulatory Protein Modification in Health and Disease. Annu Rev Biochem 82, 357, 2013.
  • 13. SUBRAMANIAN D., RAGHUNAYAKULA S., OLSEN J.V., BENINGO K.A., PASCHEN W., ZHANG X.D. Analysis of changes in SUMO-2/3 modification during breast cancer progression and metastasis. J Proteome Res 13, 3905, 2014.
  • 14. RONEN O., MALONE J.P., KAY P., BIVENS C., HALL K., PARUCHURI L.P., MO Y.Y., ROBBINS K.T., RAN S. Expression of a novel marker, Ubc9, in squamous cell carcinoma of the head and neck. Head Neck 31, 845, 2009.
  • 15. WU F., ZHU S., DING Y., BECK W.T., MO Y.Y. MicroRNA-mediated regulation of Ubc9 expression in cancer cells. Clin. Cancer Res 15, 1550, 2009.
  • 16. MOSCHOS S.J., JUKIC D.M., ATHANASSIOU C., BHARGAVA R., DACIC S., WANG X., KUAN S.F., FAYEWICZ S.L., GALAMBOS C., ACQUAFONDATA M., DHIR R., BECKER D. Expression analysis of Ubc9, the single small ubiquitin-like modifier (SUMO) E2 conjugating enzyme, in normal and malignant tissues. Hum Pathol 41, 1286, 2010.
  • 17. ZHAO Z., TAN X., ZHAO A., ZHU L., YIN B., YUAN J., QIANG B., PENG X.MicroRNA-214-mediated UBC9 expression in glioma. BMB Rep 45, 641, 2012.
  • 18. EI K., VERTEGAAL A.C.O. SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer. Trends Biochem Sci 40, 779, 2015.
  • 19. GUO W., YUAN L., XIAO Z., LIU D., ZHANG J.X. Overexpression of SUMO-1 in hepatocellular carcinoma: a latent target for diagnosis and therapy of hepatoma. J Cancer Res Clin Oncol 137, 533, 2011.
  • 20. Quality control of pesticide products, Guidelines for National Laboratories, [cited 2005] Available from : /1/ WHO_CDS_WHOPES_GCDPP_2005.15.pdf
  • 21. SPURLOCK F., LEE M. Synthetic pyrethroid use patterns, properties, and environmental effects. ACS Symp Ser 991, 3, 2008.
  • 22. MORGAN M.K. Children’s exposures to pyrethroid insecticides at home: a review of data collected in published exposure measurement studies conducted in the United States. Int. J. Environ. Res. Public Health 9, 2964, 2012.
  • 23. ERDOĞAN O., CEYHUN S.B., EKINCI D., AKSAKAL E. Impact of deltamethrin exposure on mRNA expression levels of metallothionein A, B and cytochrome P450 1A in rainbow trout muscles. Gene 484, 13, 2011.
  • 24. SAKAMOTO H., SAKAI E., FUMIMOTO R., YAMAGUCHI Y., FUKUMA Y., NISHISHITA K., OKAMOTO K., TSUKUBA T. Deltamethrin inhibits osteoclast differentiation via regulation of heme oxygenase-1 and NFATc1. Toxicol. In Vitro 26, 817, 2012.
  • 25. SHAFER T.J., MEYER D.J., CROFTON K.M. Developmental neurotoxicity of pyrethroid insecticides: Critical review and future research needs. Environ. Health Perspect 113, 123, 2005.
  • 26. WIELOGÓRSKA E., ELLIOTT C.T., DANAHER M., CANNOLI L. Endocrine disruptor activity of multiple environmental food chain contaminants. Toxicol in Vitro 29, 211, 2015.
  • 27. HU J.X., LI Y.F., LI J., PAN C., HE Z., DONG H.Y., XU L.C. Toxic effects of cypermethrin on the male reproductive system: With emphasis on the androgen receptor, Journal of applied toxicology 33 (7), 576, 2011.
  • 28. SINGH A.K., TIWARI M.N., UPADHYAY G., PATEL D.K., SINGH D., PRAKASH O., SINGH M.P. Long-term exposure to cypermethrin induces the nigrostriatal dopaminergic neurodegeneration in adult rats: Postnatal exposure enhances the susceptibility during adulthood. Neurobiol. Aging 33 (2), 404, 2010.
  • 29. AMER S.M., IBRAHIM A.A., EL-SHERBENY K.M. Induction of chromosomal aberrations and sister chromatid exchange in vivo and in vitro by the insecticide cypermethrin. Journal of Applied Toxicology 13 (5), 341, 1993.
  • 30. CARMICHAEL J., DEGRAFF W.G., GAZDAR A,F. Evaluation of a Tetrazolium-based Semiautomated Colorimetric Assay: Assessment of Chemosensitivity Testing Evaluation of a Tetrazolium-based Semiautomated Colorimetrie Assay. Assessment. Am. Assoc. Cancer Res 47, 936, 1983.
  • 31. ROSENKRANZ A.R., SCHMALDIENST S., STUHLMEIER K.M., A microplate assay for the detection of oxidative products using 2’, 7’ -dichlorofluorescindiacetate: J. Immunol. Methods 156, 39. 1992.
  • 32. DELL E.J., GANSKE F. NADH and NADPH Conversion Monitored with BMG LABTECH´s POLAR star Omega Microplate Reader. BMG LABTECH application note 170. 2008.
  • 33. GRISHAM M.B., JOHNSON G.G., LANCASTER J.R. Quantitation of nitrate and nitrite in extracellular fluids: Methods Enzymol, 268, 237, 1996.
  • 34. SCHELLER J., CHALARIS A., SCHMIDT-ARRAS D., ROSE-JOHN S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta – Mol Cell Res 1813, 878, 2011.
  • 35. NICOL L.E., GRANT W.F., COMSTOCK S.M., NGUYEN M.L., SMITH M.S., GROVE K.L ., MARKS D.L. Pancreatic inflammation and increased islet macrophages in insulin-resistant juvenile primates. J Endocrinol 217, 207, 2013.
  • 36. REHMAN H., MOHAN A., TABASSUM H., AHMAD F., RAHMAN S., PARVEZ S., RAISUDDIN S. Deltamethrin Increases Candida albicans infection susceptibility in mice. Sc and J Immunol 73, 459, 2011.
  • 37. CAO Z., SHAFER T.J., MURRAY T.F. Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons: J Pharmacol Exp Ther 336, 197, 2011.
  • 38. MARÍA D., ORTIZ-PÉREZ., TORRES-DOSAL A., BATRES LE., OLGA D., LÓPEZ-GUZMÁN., GRIMALDO M., CARRANZA C., IVÁN N., PÉREZ-MALDONADO., MARTÍNEZ F., URIZAR JP., BARRIGA FD. Environmental Health Assessment of Deltamethrin in a Malarious Area of Mexico: Environmental Persistence, Toxicokinetics, and Genotoxicity in Exposed Children. Environ Health Perspect. Jun; 113 (6), 782, 2005.
  • 39. YANG W., WANG L., ROEHN G. Small ubiquitin-like modifier 1-3 is activated in human astrocytic brain tumors and is required for glioblastoma cell survival. Cancer Science 104, 70, 2013.
  • 40. GOLEBIOWSKI F., MATIC I., TATHAM M.H., COLE C., YIN Y., NAKAMURA A., COX J., BARTON G.J., MANN M., HAY R.T. System-wide changes to SUMO modifications in response to heat shock. Science Signaling, 2 (72), 1, 2009.
  • 41. BOSSIS G., MELCHIOR F. Regulation of SUMOylation by Reversible Oxidation of SUMO Conjugating Enzymes. Mol. Cell, 21, 34, 2006.
  • 42. QU J., LIU G-H., WU K., HAN P., WANG P., LI J., Zhang X., Chen C. Nitric oxide destabilizes Pias3 and regulates sumoylation. PLoS One, 2 (10), e1085, 2007.

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