JBBS  Vol.10 No.5 , May 2020
Isoflavone Attenuates the Nuclear Transcription Factor Kappa B (NF-κB) Activation on MPP+-Induced Apoptosis of PC12 Cells
Abstract: Objective: To explore the underlying molecular mechanisms of cellular response to the challenge by 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of PC12 cells, an in vitro cell model for Parkinson’s disease, and the effect of NF-κB activation on the protection of Parkinson’s disease by Isoflavone (I). Methods: PC12 cells were used to establish the cell model of Parkinson’s disease, and are divided into five groups: control group; MPP+ group; I (Isoflavone) + MPP+ group; I group; SN-50 + MPP+ group. The content of NF-κB in PC12 cells was determined by immunocytochemistry; The viability of PC12 cells after treated with cell-permeable NF-κB inhibitor SN-50 and cell viability were measured by MTT assay; the expression levels of NF-κB p65 in cytoplasm and nuclear fractions were evaluated by western blot analysis; the mRNA expression of NF-κB p65 was analyzed by in situ hybridization (ISH). Results: Compared with the control group, the protein of NF-κB p65 both in cytoplasm and in nuclei was significantly higher than in I + MPP+ and MPP+ groups; similarly, the mRNA expression level of NF-κB p65 gene was also significantly higher; moreover, the protein expression of NF-κB p65 was much lower in I group (P < 0.05). In addition, compared with the MPP+ group, the protein of NF-κB p65 was significantly lower in I + MPP+ group, the mRNA expression level of NF-κB p65 gene was also significantly lower, and the protein expression level of NF-κB p65 was much lower in I + MPP+ group (P < 0.05); however, there was no significant difference between control group and I + MPP+ group (P > 0.05). Conclusion: NF-κB activation is essential to MPP+-induced apoptosis in PC12 cells; but Isoflavone can inhibit the cell damage to some extent to execute its protective function, which may be involved in nigral neurodegeneration in patients with Parkinson’s disease.
Cite this paper: Cheng, W. , Huang, A. , Zhang, L. , Feng, D. , Sun, X. , Xu, H. , Sun, Q. and Li, X. (2020) Isoflavone Attenuates the Nuclear Transcription Factor Kappa B (NF-κB) Activation on MPP+-Induced Apoptosis of PC12 Cells. Journal of Behavioral and Brain Science, 10, 191-199. doi: 10.4236/jbbs.2020.105012.

[1]   Gomezc, R.J., Rique, M., et al. (2001) Low Concentration of 1-methyl-4-phenylpyri-diniumion Induce Caspase Mediated Apoptosis in Human SH-SY5Y Neuroblastoma Cells. Journal of Neuroscience Research, 63, 421-428.<421::AID-JNR1037>3.0.CO;2-4

[2]   Hunot, S., Brugg, B., Ricard, D., et al. (1997) Nuclear Translocation of NF-kB Is Increased in Dopaminergic Neurons in Patients. Proceedings of the National Academy of Sciences of the United States of America, 94, 7531-7536.

[3]   Chinopiulos, C. and Adam-Vizi, V. (2001) Mitochondria Deficient in Complex I Activity Are Depolarized by Hydrogen peroxide in Nerve Terminals Relevance to Parkinson’s Disease. Journal of Neurochemistry, 76, 302-306.

[4]   Hauahan, D., Clark, E.T., Kuchibhotla, J., Gewertz. B.L. and Collins, T. (1995) E-select in Gene Induction by Conizing Radiation Is Independent of Cytokine Induction Biochem. Biochemical and Biophysical Research Communications, 217, 784-795.

[5]   Lipton, S.A. (1997) Janus Faces of NF-kB. Neurodestruction versus Neuroprotection. Nature Medicine, 3, 20-22.

[6]   Jing, H., Wang, S., Wang, M., Fu, W., Zhang, C. and Xu, D. (2017) Isobavachalcone Attenuates MPTP-Induced Parkinson’s Disease in Mice by Inhibition of Microglial Activation through NF-κB Pathway. PLoS ONE, 12, e0169560.

[7]   Grünblatt, E., Mandel, S. and Youdim, M.B. (2000) Neuroprotective strategies in Parkinson’s Disease Using the Models of 6-hydroxydopamine and MPTP. Annals of the New York Academy of Sciences, 899, 262-273.

[8]   Kim, B.W., Koppula, S., Kumar, H., Park, J.Y., Kim, I.W., More, S.V., Kim, I.S., Han, S.D., Kim, S.K., Yoon, S.H. and Choi, D.K. (2017) Corrigendum to “α-Asarone Attenuates Microglia-Mediated Neuroinflammation by Inhibiting NF Kappa B Activation and Mitigates MPTP-Induced Behavioral Deficits in a mouse Model of Parkinson’s Disease” [Neuropharm 97 (2015) 46-57]. Neuropharmacology, 116, 444-445.

[9]   Feuillard, J., Schuhmacher, M., Kohanna, S., et al. (2000) Inducible Loss of NF-kB Activity Is Associated with Apoptosis and bcl-2 Down Regulation in Epstein-Barr Virus-Transformed B Lympho-cytes. Blood, 95, 2068-2075.

[10]   Aylialatela, G., Kaufman, J.A., Trevino, A., et al. (1998) Central Nervous System DNA Fragmentation Induced by the Inhibition of Nuclear Factor Kappa B. Neuroreport, 9, 489-493.

[11]   Li, X.L. and Sun, S.G., et al. (2003) Estrogen Protect PC12 Cells Induced by MPTP. Chinese Journal of Neurology, 36, 324-327.

[12]   Li, X.L. and Sun, S.G., et al. (2003) The Neuroprotective Strategies of Estrogen in Parkinson’s Disease. Chinese Journal of Neuroimmunology and Neurology, 10, 254-257.

[13]   Panet, H., Barzilai, A., Daily, D., et al. (2001) Activation of Hudeat Transcription Factor Kappa B (NF-kB) Is Essential for Dopamine Induced Apoptosis in PC12 Cells. Journal of Neurochemistry, 77, 391-398.

[14]   Mitra, S., Ghosh, N., Sinha, P., Chakrabarti, N. and Bhattacharyya, A. (2016) Alteration of Nuclear Factor-Kappa B Pathway Promote Neuroinflammation Depending on the Functions of Estrogen Receptors in Substantia Nigra after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Treatment. Neuroscience Letters, 616, 86-92.