Neuroprotective Role of SRT1720 Against Hydrogen Peroxide Induced Oxidative Stress in NT2 Cells

Authors

  • Lama N. Abdullah Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA, USA
  • Ruy Tchao Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA, USA
  • Shanaz M. Tejani-Butt Department of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA, USA

Keywords:

Oxidative stress, H2O2, SRT1720, NT2 cells

Abstract

Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by a significant increase in neuronal loss. Oxidative stress (OS) plays a significant role on neuronal damage. Reactive oxygen species (ROS) generated from agents such as hydrogen peroxide (H2O2) leads to cell damage and reduction of cell viability. Sirtuin 1 (SIRT1) is a therapeutic target for neurodegenerative disorders because it regulates several cellular functions and biological processes that promote cellular longevity. This study was undertaken to examine the role of SRT1720 in protecting cells from H2O2 induced stress in Ntera-2 cl.D1(NT2), which has been proven to be a useful in vitro system for the investigation of functions related to human neuronal and glial systems. The results provide evidence that H2O2 significantly induced oxidative stress in a concentration dependent manner. Moreover, pre-treatment with low concentrations of SRT1720 for 48 hours protected against the effects of H2O2. Also, a combination of H2O2 and SRT1720 improved cell viability. Interestingly, apoptotic or necrotic cell death was not detected after H2O2 treatment in the cell culture model system employed.

References

. Peña-Bautista, C., Baquero, M., Vento, M., and Cháfer-Pericás, C. Free radicals in Alzheimer’s disease: Lipid peroxidation biomarkers. Clinica Chimica Acta, vol. 491, pp. 85-90, 2019.

. Dai, S.H., Chen, T., Wang, Y.H., Zhu, J., Luo, P., Rao, W., Yang, Y.F., Fei, Z. and Jiang, X.F. Sirt3 attenuates hydrogen peroxide-induced oxidative stress through the preservation of mitochondrial function in HT22 cells. International Journal of Molecular Medicine, vol. 34(4), pp. 1159-1168, 2014.

. Guo, C., Sun, L., Chen, X., & Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural regeneration research, vol. 8(21), pp. 2003–2014, 2013.

. Chi, H., Chang, H. Y., & Sang, T. K. Neuronal Cell Death Mechanisms in Major Neurodegenerative Diseases. Int J Mol Sci, vol. 19(10), pp. 3082, 2018.

. Xu, Y., Gao, Y. W., and Yang, Y. SC79 protects dopaminergic neurons from oxidative stress. Oncotarget, vol. 9(16), pp. 12639–12648, 2017.

. Mei, Z., Zhang, X., Yi, J., Huang, J., He, J., and Tao, Y. Sirtuins in metabolism, DNA repair and cancer. Journal of experimental & clinical cancer research, vol. 35(1), pp. 182, 2016.

. Jęśko, H., Wencel, P., and Strosznajder, R.P. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochem Res, vol. 42(3), pp. 876–890, 2017.

. Gomes BAQ, Silva JPB, Romeiro CFR, Dos Santos SM, Rodrigues CA, Gonçalves PR, Sakai JT, Mendes PFS, Varela ELP, and Monteiro MC. Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT1. Oxid Med Cell Longev, vol. 2018, pp. 1-15, 2018.

. Cai, Y., Xu, L., Xu, H. and Fan, X. SIRT1 and Neural Cell Fate Determination. Molecular Neurobiology, vol. 53(5): pp. 2815-2825, 2015.

. Pacholec, M., Bleasdale, J.E., Chrunyk, B., Cunningham, D., Flynn, D., Garofalo, R.S., Griffith, D., Griffor, M., Loulakis., P., Pabst, B., Qiu, X., Stockman, B., Thanabal, V., Varghese, A., Ward, J., Withka, J., and Ahn, K. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem, vol. 285(11), pp. 8340-8351, 2010.

. Fanibunda, S.E., Deb, S., Maniyadath, B., Tiwari, P., Ghai, U., Gupta, S., Figueiredo, D., Weissataub, N., Gingrich, J.A., Vaidya, A.D.B., Kolthur-seetharan, U., and Vaidya, V.A. Serotonin regulates mitochondrial biogenesis and function in rodent cortical neurons via the 5-HT2A receptor and SIRT1-PGC-1α axis. Proceedings of the National Academy of Sciences, vol. 116(22), pp. 11028-11037, 2019.

. Tamango, E., Aragno, M., Parola, M., Parola, S., Brignardello, E., Boccuzzi, G., and Danni, O. NT2 neurons, a classical model for Alzheimer's disease, are highly susceptible to oxidative stress, vol. 11(9), pp. 1865-18659, 2000.

. CyQUANT® Cell Proliferation Assay Kit. Internet: https://assets.thermofisher.com/TFS-Assets/LSG/manuals/mp07026.pdf, 2006, [July. 22, 2020].

. Muse® Annexin V and Dead Cell Assay Kit. Internet: https://www.bmbio.com/Portals/0/product/upload/MCH100105_2.pdf, 2013, [July. 22, 2020].

. LIVE/DEAD ® Viability/Cytotoxicity Kit *for mammalian cells*. Internet: https://www.thermofisher.com/document-connect/document-connect.html?url=https%3A%2F%2Fassets.thermofisher.com%2FTFS-Assets%2FLSG%2Fmanuals%2Fmp03224.pdf&title=TElWRSYjNDc7REVBRCBWaWFiaWxpdHkmIzQ3O0N5dG90b3hpY2l0eSBLaXQ=, 2005, [July. 22, 2020].

. PrestoBlue® Cell Viability Reagent Kit, Internet: https://www.thermofisher.com/document-connect/document-connect.html?url=https%3A%2F%2Fassets.thermofisher.com%2FTFS-Assets%2FLSG%2Fmanuals%2FMAN0018370-PrestoBlueCellViabilityReagent-PI.pdf&title=UHJvZHVjdCBTaGVldDogUHJlc3RvQmx1ZSBDZWxsIFZpYWJpbGl0eSBSZWFnZW50, 2019. [July. 22, 2020].

. Takeichi, M & Okada, T.S. Roles of magnesium and calcium ions in cell-to-substrate adhesion. Experimental Cell Research, vol. 74(1), pp. 51-60,1972.

. Whittemore, E.R., Loo, D.T., Watt, J.A., and Cotmans, C.W. A detailed analysis of hydrogen peroxide-induced cell death in primary neuronal culture. Neurosciences, vol. 67(4), pp. 921-932, 1995.

. Rodriguez, R., Fernandez, A. and Fraga, M. Role of Sirtuins in Stem Cell Differentiation. Genes & Cancer, vol. 4(3-4), pp. 105-111, 2013.

. Cai, A. L., Zipfel, G. J. and Sheline, C.T. Zinc neurotoxicity is dependent on intracellular NAD+ levels and the sirtuin pathway. European Journal of Neuroscience, vol. 24(8), pp. 2169–2176, 2006.

. Yeung, F., Hoberg, J.E., and Ramsey, C.S. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. The EMBO Journal, vol. 23(12), pp. 2369-2380, 2004.

. Tang, B.L. Sirt1 and the Mitochondria. Molecules and Cells, vol. 39(2), pp. 87-95, 2016.

. Mesbah-Ardekani, M., Homayouni-Moghaddam, F., Rezvani, M. and Izadi, M. Effects of Hydrogen Peroxide Oxidative Stress on the Pattern of Pro-apoptotic and Anti-apoptotic Genes Expression during PC12 Cells Differentiation. International Journal of Medical Laboratory, vol. 2(3), pp. 158-167, 2015.

. Yang, Y., Hsieh, T., and Tsai, M. Neuroprotective effects of Hu-Yi-Neng, a diet supplement, On SH-SY5Y human neuroblastoma cells. J Nutr Health Aging, vol. 18, pp. 184–190, 2014.

. Somayajulu, M., McCarthy, S., Hung, M., Sikorska, M., Borowy-Borowski, H., and Pandey, S. Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10. Neurobiology of disease, vol.18(3), pp. 618-627, 2005.

. Liu, D., Croteau, D. L., Souza-Pinto, N., Pitta, M., Tian, J., Wu, C., Jiang, H., Mustafa, K., Keijzers, G., Bohr, V. A., & Mattson, M. P. Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 31(2), pp. 680–692, 2011.

. Lia, D., Reyes, A., de Melo Campos, J.T.A., Piolot, T., Radicella, J.P, and Campalans, A. Mitochondrial maintenance under oxidative stress depends on mitochondrially localised α-OGG1. J Cell Sci, vol. 131(12), 2018.

. Yang, J. L., Weissman, L., Bohr, V. A., & Mattson, M. P. Mitochondrial DNA damage and repair in neurodegenerative disorders. DNA repair, vol. 7(7): pp. 1110–1120, 2008.

Downloads

Published

2020-08-03

How to Cite

N. Abdullah , L. ., Tchao, R. ., & M. Tejani-Butt, S. . (2020). Neuroprotective Role of SRT1720 Against Hydrogen Peroxide Induced Oxidative Stress in NT2 Cells. International Journal of Sciences: Basic and Applied Research (IJSBAR), 53(1), 212–225. Retrieved from https://www.gssrr.org/index.php/JournalOfBasicAndApplied/article/view/11524

Issue

Vol. 53 No. 1 (2020)

Section

Articles

License

Authors who submit papers with this journal agree to the following terms.