Abstract
Amyloid beta-protein (Aβ) is involved in the pathogenesis of Alzheimer’s disease (AD). Aβ induces free radical production in neuronal cells, leading to oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK), extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown to have protection to several models of neurodegenerative diseases by its antioxidant and anti-inflammatory properties. In the present study, we examined the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) on Aβ1–42 induced cytotoxicity of PC12 cells. Aβ1–42 induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells. The effect of BBD on these harmful factors and the related signaling pathways were examined by biochemical and western blot assays. The result showed that BBD protected PC12 cells from Aβ1–42 induced cytotoxicity with the increased cell viability and acetylcholine release, and the decreased lactate dehydrogenase, malondialdehyde and calcium release. BBD significantly reduced Aβ-induced JNK, ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the neuroprotective effect of BBD on Aβ-induced cytotoxicity was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of AD.
Similar content being viewed by others
References
Borovikova, L.V., S. Ivanova, M. Zhang, H. Yang, G.I. Botchkina, H.N. Abumrad, J.W. Eaton, and K.J. Tracey. 2000. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458–462.
Bournival, J., P. Quessy, and M.G. Martinoli. 2009. Protective effects of resveratrol and quercetin against MPP+ -induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Molecule Neurobiology 29: 1169–1180.
Drukarch, B., E. Schepens, J.C. Stoof, C.H. Langeveld, and F.L. Van Muiswinkel. 1998. Astrocyte-enhanced neuronal survival is mediated by scavenging of extracellular reactive oxygen species. Free Radical Biology and Medicine 25: 217–220.
Floyd, R.A. 1999. Antioxidants, oxidative stress, and degenerative neurological disorders. Proceeding Society Experimental Biology and Medicine 222: 236–245.
Forman, M.S., J.Q. Trojanowski, and V.M. Lee. 2004. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nature Medicine 10: 1055–1063.
Hou, R.C., H.M. Huang, J.T. Tzen, and K.C. Jeng. 2003. Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells. Journal of Neuroscience Research 74: 123–133.
Hou, C.W., Y.L. Chen, S.H. Chuang, and K.C. Jeng. 2014. Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on ischemic and hypoxic neuronal injury. Journal of Biomedical Science 21: 15.
Hu, J.F., S.F. Chu, N. Ning, Y.H. Yuan, W. Xue, N.H. Chen, and J.T. Zhang. 2010. Protective effect of (−) Clausenamide against Aβ-induced neurotoxicity in differentiated PC12 cells. Neuroscience Letters 483: 78–82.
Huang, H.M., Ou Hsio-Chung, and S.J. Hsieh. 2000. Antioxidants prevent amyloid peptide-induced apoptosis and alteration of calcium homeostasis in cultured cortical neurons. Life Science 66: 1879–1892.
Huang, T.C., K.T. Lu, Y.Y. Wo, Y.J. Wu, and Y.L. Yang. 2011. Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation. PLoS One 6: e29102.
Hwang, S.L., and G.C. Yen. 2008. Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. Journal of Agriculture and Food Chemistry 56: 859–864.
Jang, J.H., and Y.J. Surh. 2005. Beta-amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase-NF-kappaB signaling pathway. Free Radical Biology and Medicine 38: 1604–1613.
Jeong, J.H., H.R. Jeong, Y.N. Jo, H.J. Kim, J.H. Shin, and H.J. Heo. 2013. Ameliorating effects of aged garlic extracts against Aβ-induced neurotoxicity and cognitive impairment. BMC Complementary and Alternative Medicine 13: 268.
Khodadadi, S., G.H. Riazi, S. Ahmadian, E. Hoveizi, O. Karima, and H. Aryapour. 2012. Effect of N-homocysteinylation on physicochemical and cytotoxic properties of amyloid beta-peptide. FEBS Letters 586: 127–131.
Kudo, W., H.P. Lee, M.A. Smith, X. Zhu, S. Matsuyama, and H.G. Lee. 2012. Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity. Cell Death and Disease 3: e309.
Li, G., R. Ma, C. Huang, Q. Tang, Q. Fu, H. Liu, B. Hu, and J. Xiang. 2008. Protective effect of erythropoietin on beta-amyloid-induced PC12 cell death through antioxidant mechanisms. Neuroscience Letters 442: 143–147.
Lievre, V., P. Becuwe, and A. Bianchi. 2001. Intracellular generation of free radicals and modifications of detoxifying enzymes in cultured neurons from the developing rat forebrain in response to transient hypoxia. Neuroscience 105: 287–297.
Muthaiyah, B., M.M. Essa, V. Chauhan, and A. Chauhan. 2011. Protective effects of walnut extract against amyloid beta peptide-induced cell death and oxidative stress in PC12 cells. Neurochemical Research 36: 2096–2103.
Nordberg, A. 2004. Functional studies of cholinergic activity in normal and Alzheimer disease states by imaging technique. Progress in Brain Research 145: 301–310.
Nozaki, K., M. Nishimura, and N. Hashimoto. 2001. Mitogen-activated protein kinases and cerebral ischemia. Molecule Neurobiology 23: 1–19.
Pagani, L., and A. Eckert. 2011. Amyloid-Beta interaction with mitochondria. International Journal Alzheimers Disease 2011: 925050.
Ramin, M., P. Azizi, F. Motamedi, A. Haghparast, and F. Khodagholi. 2011. Inhibition of JNK phosphorylation reverses memory deficit induced by β-amyloid (1-42) associated with decrease of apoptotic factors. Behavioural Brain Research 217: 424–431.
Regan, R.F., Y. Wang, X. Ma, A. Chong, and Y. Guo. 2001. Activation of extracellular signal-regulated kinases potentiates hemin toxicity in astrocyte cultures. Journal of Neurochemistry 79: 545–555.
Selkoe, D.J. 2008. Soluble oligomers of the amyloid β-protein impair synaptic plasticity and behavior. Behavioural Brain Research 192: 106–113.
Shanks, M., M. Kivipelto, R. Bullock, and R. Lane. 2009. Cholinesterase inhibition: Is there evidence for disease-modifying effects? Current Medical Research and Opinion 25: 2439–2446.
Suen, K.C., K.F. Lin, W. Elyaman, K.F. So, R.C. Chang, and J. Hugon. 2003. Reduction of calcium release from the endoplasmic reticulum could only provide partial neuroprotection against beta-amyloid peptide toxicity. Journal of Neurochemistry 87: 1413–1426.
Taepavarapruk, P., and C. Song. 2010. Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1beta administrations: Effects of omega-3 fatty acid EPA treatment J. Journal of Neurochemistry 112: 1054–1064.
Tanzi, R.E., and L. Bertram. 2005. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120: 545–555.
Wang, R., J. Zhou, and X.C. Tang. 2002. Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells. Molecular Brain Research 107: 1–8.
Xiao, X.Q., R. Wang, and X.C. Tang. 2000. Huperzine A and tacrine attenuate β-amyloid peptide-induced oxidative injury. Journal of Neuroscience Research 61: 564–569.
Yan, M.H., X. Wang, and X. Zhu. 2013. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. Free Radical Biology and Medicine 62: 90–101.
Zhang, H.Y., X.C. Tang, and B. Huperzine. 2000. A novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neuroscience Letters 292: 41–44.
Acknowledgments
This work was supported in part by a Grant TTMHH103R0004 from Tung’s Taichung MetroHarbor Hospital and a research grant from Yuanpei University.
Conflict of interest
The authors have no financial conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hou, CW., Chang, SY. & Jeng, KC. Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on Aβ-stressed PC12 cells. Arch. Pharm. Res. 38, 543–548 (2015). https://doi.org/10.1007/s12272-014-0426-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-014-0426-1