Share This Article:

Reactive oxygen species induced oxidative stress, neuronal apoptosis and alternative death pathways

Abstract Full-Text HTML XML Download Download as PDF (Size:340KB) PP. 14-21
DOI: 10.4236/abb.2013.41003    4,422 Downloads   7,636 Views   Citations

ABSTRACT

Reactive oxygen species (ROS) are produced as a byproduct of cellular metabolic pathways and function as a critical second messenger in a variety of intracellular signaling pathways. The excessive intracellular generation of ROS on the other renders a cell oxidatively stressed. This involvement of ROS in numerous diseases has been documented and at different phases of the apoptotic pathway such as induction of mitochondrial permeability transition and release of mitochondrial death amplification factors, activetion of intracellular caspases and DNA damage has been clearly established. Cell death by apoptosis is a part of normal development and maintenance of tissue homeostasis. Polychlorinated biphenyls, one of the environmental pollutants which are widely used in electrical industries and lipophilic and resistant to biological decomposition accumulate through food chain. They are developmental neurotoxicants which induce neuronal apoptosis. Our studies proved that oxidative stress is induced promoting LPO and a decrease in all the antioxidant enzymes in testis, epididymis, ventral prostate, seminal vesicles, liver, kidney and brain regions. Neuronal damages were observed in all the brain regions after PCB exposure. PCB increased caspase8 mRNA/protein expression in hippocampus of adult rats. This upregulation results in Fas-FasL mediated induction of hippocampal apoptosis. Performin/granzyme induced apoptosis is the main pathway used by cytotoxic lymphocytes to eliminate virus-infected or transformed cells. The production of ROS is greatly increased during reperfusion phase when oxygen becomes available and the mitochondrial respiratory chain is impaired. Furthermore, this is exacerbated by reduced antioxidant defenses.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Selvakumar, K. , Krishnamoorthy, G. , Venkataraman, P. and Arunakaran, J. (2013) Reactive oxygen species induced oxidative stress, neuronal apoptosis and alternative death pathways. Advances in Bioscience and Biotechnology, 4, 14-21. doi: 10.4236/abb.2013.41003.

References

[1] Okouchi, M., Ekshyyan, O., Maracine, M. and Aw, T.Y. (2007) Neuronal apoptosis in neurodegeneration. Antioxidant and Redox Signaling, 9, 1059-1096. doi:10.1089/ars.2007.1511
[2] Loddick, S.A. and Rothwell, N.J. (1999) Mechanisms of tumor necrosis factor action on neurodegeneration: Interaction with insulin-like growth factor-1. Proceedings of National Academy of Sciences USA, 96, 9449-9451. doi:10.1073/pnas.96.17.9449
[3] Safe, S.H. (1994) Polychlorinated biphenyls (PCBs): Environmental impact, biochemical and toxic responses, and implications for risk assessment. Critical Reviews in Toxicology, 24, 87-149. doi:10.3109/10408449409049308
[4] Kamrin, M.A. and Ringer, R.K. (1994) PCB residues in mammals: A review. Toxicology and Environmental Chemistry, 41, 63-84. doi:10.1080/02772249409357961
[5] Mariussen, E. and Fonnum, F. (2001) The effect of polychlorinated biphenyls on the high affinity uptake of the neurotransmitters, dopamine, serotonin, glutamate and GABA, into rat brain synaptosomes. Toxicology, 159, 11-21. doi:10.1016/S0300-483X(00)00374-7
[6] Widholm, J.J., Clarkson, G.B., Strupp, B.J., Crofton, K.M., Seegal, R.F. and Schantz, S.L. (2001) Spatial reversal learning in Aroclor 1254-exposed rats: Sex-specific deficits in associative ability and inhibitory control. Toxicology and Applied Pharmacology, 174, 188-198. doi:10.1006/taap.2001.9199
[7] Pravettoni, A., Colciago, A., Negri-Cesi, P., Villa, S. and Celotti, F. (2005) Ontogenetic development, sexual differentiation, and effects of Aroclor 1254 exposure on expression of the arylhydrocarbon receptor and of the arylhydrocarbon receptor nuclear translocator in the rat hypothalamus. Reproductive Toxicology, 20, 521-530. doi:10.1016/j.reprotox.2005.03.008
[8] Engel, R.H. and Evens, A.M. (2006) Oxidative stress and apoptosis: a new treatment paradigm in cancer. Frontiers in Biosciences, 11, 300-312. doi:10.2741/1798
[9] Korrick, S.A. and Sagiv, S.K. (2008) Polychlorinated biphenyls, organochlorine pesticides and neurodevelopment. Current Opinion in Pediatrics, 20, 198-204. doi:10.1097/MOP.0b013e3282f6a4e9
[10] Halliwell, B. and Gutteridge, J. (1999) Free Radicals in Biology and Medicine. Oxford University Press, New York,
[11] Pajovic, S.B., Saicic, Z.S., Spasic, M.B. and Petrovic, V.M. (2003), The effect of ovarian hormones on antioxidant enzyme activities in the brain of male rats. Physiological Research, 52, 189-194.
[12] Anbalagan, J., Kanagaraj, P., Srinivasan, N., Aruldhas, M.M. and Arunakaran, J. (2003) Effect of polychlorinated biphenyl, Aroclor 1254 on rat epididymis. Indian Journal of Medical Research, 118, 236-242.
[13] Venkataraman, P., Sridhar, M., Dhanammal, S., Vijayababu, M.R., Srinivasan, N. and Arunakaran, J. (2004) Antioxidant role of zinc in PCB (Aroclor 1254) exposed ventral prostate of albino rats. Journal of Nutritional Biochemistry, 15, 608-613. doi:10.1016/j.jnutbio.2004.06.001
[14] Murugesan, P., Kanagaraj, P., Yuvaraj, S., Balasubramanian, K., Aruldhas, M.M. and Arunakaran, J. (2005) The inhibitory effects of polychlorinated biphenyl Aroclor 1254 on Leydig cell LH receptors, steroidogenic enzymes and antioxidant enzymes in adult rats. Reproductive Toxicology, 20, 117-126. doi:10.1016/j.reprotox.2004.11.011
[15] Banudevi, S., Krishnamoorthy, G., Venkataraman, P., Vignesh, R.C., Aruldhas, M.M. and Arunakaran, J. (2006) Role of alpha-tocopherol on antioxidant status in liver, lung and kidney of PCB exposed male albino rats. Food and Chemical Toxicology, 44, 2040-2046. doi:10.1016/j.fct.2006.07.017
[16] Venkataraman, P., Krishnamoorthy, G., Vengatesh, G., Srinivasan, N., Aruldhas, M.M. and Arunakaran, J. (2008) Protective role of melatonin on PCB (Aroclor 1,254) induced oxidative stress and changes in acetylcholine esterase and membrane bound ATPases in cerebellum, cerebral cortex and hippocampus of adult rat brain. International Journal of Developmental Neuroscience, 26, 585-591. doi:10.1016/j.ijdevneu.2008.05.002
[17] Selvakumar, K., Bavithra, S., Suganthi, M., Benson, C.S., Elumalai, P., Arunkumar, R., Krishnamoorthy, G., Venkataraman, P. and Arunakaran, J. (2012) Protective role of quercetin on PCBs-induced oxidative stress and apoptosis in hippocampus of adult rats. Neurochemical Research, 37, 708-721. doi:10.1007/s11064-011-0661-5
[18] Huang, C., Chen, X., Guo, B., Huang, W., Shen, T., Sun, X., Xiao, P. and Zhou, Q. (2012) Induction of Apoptosis by Icariside II through Extrinsic and Intrinsic Signaling Pathways in Human Breast Cancer MCF7 Cells. Bioscience Biotechnology and Biochemistry, 76, 1322-1328. doi:10.1271/bbb.120077
[19] Lee, S.H., Shin, M.S., Park, W.S., Kim, S.Y., Kim, H.S., Lee, J.H., Han, S.Y., Lee, H.K., Park, J.Y., Oh, R.R., Jang, J.J., Lee, J.Y. and Yoo, N.J. (1999) Immunohistochemical localization of FAP-1, an inhibitor of Fas-mediated apoptosis, in normal and neoplastic human tissues. Acta Pathologica, Microbiologica et Immunologica Scandinavica, 107, 1101-1108. doi:10.1111/j.1699-0463.1999.tb01515.x
[20] Saradha, B., Vaithinathan, S. and Mathur, P.P. (2009) Lindane induces testicular apoptosis in adult Wistar rats through the involvement of Fas-FasL and mitochondria-dependent pathways. Toxicology. 255, 131-139. doi:10.1016/j.tox.2008.10.016
[21] Krishnamoorthy, G., Selvakumar, K., Elumalai, P., Venkataraman, P. and Arunakaran, J. (2011) Protective role of lycopene on polychlorinated biphenyls (Aroclor 1254)-induced adult rat Sertoli cell dysfunction by increased oxidative stress and endocrine disruption, Biomedicine and Preventive Nutrition, 1, 116-125. doi:10.1016/j.bionut.2011.03.001
[22] Nagata, S. (1999) Fas ligand-induced apoptosis. Annual Reviews in Genetics, 33, 29-55. doi:10.1146/annurev.genet.33.1.29
[23] Hengartner, M.O. and Bryant, J.A. (2005) Apoptotic cell death: From worms to wombats ...but what about the weeds? Symposium on Society of Experimental Biology, 52, 1-12.
[24] Kreuz, S., Siegmund, D., Rumpf, J.J., Samel, D., Leverkus, M., Janssen, O., Hacker, G., Dittrich-Breiholz, O., Kracht, M., Scheurich, P. and Wajant, H. (2004) NFkappaB activation by Fas is mediated through FADD, caspase-8, and RIP and is inhibited by FLIP. Journal of Cell Biology, 166, 369-380. doi:10.1083/jcb.200401036
[25] Kaur, M., Pop, M., Shi, D., Brignone, C. and Grossman, S.R. (2006) hHR23B is required for genotoxic-specific activation of p53 and apoptosis. Oncogene, 26, 1231-1237. doi:10.1038/sj.onc.1209865
[26] Jacobson, M.D. (1997). Programmed cell death: A missing link is found. Trends in Cellular Biology, 7, 467-469. doi:10.1016/S0962-8924(97)01182-3
[27] Mariussen, E. and Fonnum, F. (2006) Neurochemical targets and behavioral effects of organohalogen compounds: An update. Critical Reviews in Toxicology, 36, 253-289. doi:10.1080/10408440500534164
[28] Martin, L.J. (2011) Mitochondrial pathobiology in ALS. Journal of Bioenergetics and Biomembrane, 43, 569-579. doi:10.1007/s10863-011-9395-y
[29] Sánchez-Alonso, J.A., López-Aparicio, P., Recio, M.N. and Pérez-Albarsanz, M.A. (2004) Polychlorinated biphenyl mixtures (Aroclors) induce apoptosis via Bcl-2, Bax and caspase-3 proteins in neuronal cell cultures. Toxicology Letters, 153, 311-326. doi:10.1016/j.toxlet.2004.05.012
[30] Mariussen, E., Myhre, O., Reistad, T. and Fonnum, F. (2002) The polychlorinated biphenyl mixture aroclor 1254 induces death of rat cerebellar granule cells: The involvement of the N-methyl-D-aspartate receptor and reactive oxygen species. Toxicology and Applied Pharmacology, 179, 137-144. doi:10.1006/taap.2002.9353
[31] Kass, G.E. and Orrenius, S. (1999) Calcium signaling and cytotoxicity. Environmental and Health Perspectives. 107, 25-35.
[32] Tilson, H.A., Kodavanti, P.R., Mundy, W.R. and Bushnell, P.J. (1998) Neurotoxicity of environmental chemicals and their mechanism of action. Toxicology Letters, 102-103, 631-635. doi:10.1016/S0378-4274(98)00271-9
[33] Baliga, B.C. and Kumar, S. (2002) Role of Bcl-2 family of proteins in malignancy. Journal of Hematology Oncology, 20, 63-74. doi:10.1002/hon.685
[34] Gross, A., McDonnell, J.M. and Korsmeyer, S.J. (1999) BCL-2 family members and the mitochondria in apoptosis. Genes and Development, 13, 1899-1911. doi:10.1101/gad.13.15.1899
[35] Hofmann, K. (1999) The modular nature of apoptotic signaling proteins. Cellular and Molecular Life Sciences, 55, 1113-1128. doi:10.1007/s000180050361
[36] Podack, E.R., Young, J.D. and Cohn, Z.A. (1985) Isolation and biochemical and functional characterization of perforin 1 from cytolytic T-cell granules. Proceeding of National Academy of Science USA, 82, 8629-8633. doi:10.1073/pnas.82.24.8629
[37] Yasukawa, M., Ohminami, H., Arai, J., Kasahara, Y., Ishida, Y. and Fujita, S. (2000) Granule exocytosis, and not the fas/fas ligand system, is the main pathway of cytotoxicity mediated by alloantigen-specific CD4(+) as well as CD8(+) cytotoxic T lymphocytes in humans. Blood, 95, 2352-2355.
[38] Trapani, J.A. and Smyth, M.J. (2002) Functional significance of the perforin/granzyme cell death pathway. Nature Reviews in Immunology, 2, 735-747.
[39] Nakajima, H., Park, H.L. and Henkart, P.A. (1995) Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. Journal of Experimental Medicine, 181, 1037-1046. doi:10.1084/jem.181.3.1037
[40] Shi, L., Kam, C.M., Powers, J.C., Aebersold, R. and Greenberg, A.H. (1992) Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. Journal of Experimental Medicine, 176, 1521-1529. doi:10.1084/jem.176.6.1521
[41] Brunner, T., Wasem, C., Torgler, R., Cima, I., Jakob, S. and Corazza, N. (2003) Fas (CD95/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Seminars in Immunology, 15, 167-176. doi:10.1016/S1044-5323(03)00035-6
[42] Pardo, J., Bosque, A., Brehm, R., Wallich, R., Naval, J., Müllbacher, A., Anel, A. and Simon, M.M. (2004) Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis. Journal of Cell Biology, 167, 457-468. doi:10.1083/jcb.200406115
[43] Sakahira, H., Enari, M. and Nagata, S. (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature, 391, 96-99. doi:10.1038/34214
[44] Barry, M. and Bleackley, R.C., (2002) Cytotoxic T lymphocytes: All roads lead to death. Nature Reviews in Immunology, 2, 401-409.
[45] Russell, J.H. and Ley, T.J. (2002) Lymphocyte-mediated cytotoxicity. Annual Reviews in Immunology, 20, 323-370. doi:10.1146/annurev.immunol.20.100201.131730
[46] Goping, I.S., Barry, M., Liston, P., Sawchuk, T., Constantinescu, G., Michalak, K.M., Shostak, I., Roberts, D.L., Hunter, A.M., Korneluk, R. and Bleackley, R.C. (2003) Granzyme B-induced apoptosis requires both direct caspase activation and relief of caspase inhibition. Immunity 18, 355-365. doi:10.1016/S1074-7613(03)00032-3
[47] Devadas, S., Das, J., Liu, C., Zhang, L., Roberts, AI., Pan, Z., Moore, P.A., Das, G. and Shi, Y. (2006) Granzyme B is critical for T cell receptor-induced cell death of type 2 helper T cells. Immunity, 25, 237-247. doi:10.1016/j.immuni.2006.06.011
[48] Heusel, J.W., Wesselschmidt, R.L., Shresta, S., Russell, J.H. and Ley, T.J. (1994) Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells. Cell, 76, 977-987. doi:10.1016/0092-8674(94)90376-X
[49] Alimonti, J.B., Shi, L., Baijal, P.K. and Greenberg, A.H. (2001) Granzyme B induces BID-mediated cytochrome c release and mitochondrial permeability transition. Journal of Biological Chemistry, 276, 6974-6982. doi:10.1074/jbc.M008444200
[50] Lieberman, J., (2003) The ABCs of granule-mediated cytotoxicity: New weapons in the arsenal. Nature Reviews in Immunology, 3, 361-370. doi:10.1038/nri1083
[51] Gil-Parrado, S., Fernandez-Montalvan, A., Assfalg-Machleidt, I., Popp, O., Bestvater, F., Holloschi, A., Knoch, T.A., Auerswald, E.A., Welsh, K. and Reed, J.C. (2002) Ionomycin-activated calpain kitriggers apoptosis. A probable role for Bcl-2 family members. Journal of Biological Chemistry, 277, 27217-27226. doi:10.1074/jbc.M202945200
[52] Cuadrado, I., Fernandez-Velasco, M., Bosca, L. and de Las Heras B (2011) Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: Involvement of AKT activation. Cell Death and Diseases, 2, e229. doi:10.1038/cddis.2011.113

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.