MPP+ Attenuates the Inhibition of p53 by Parkin in SH-SY5Y Cells

Author(s): Yanmin Zhong

Parkin acts as a p53 transcriptional repressor, binds to p53 gene promoter in the nucleus, thereby inhibiting the transcription of p53 gene. However, whether this process take part in Parkinson's disease (PD) is unclear. In order to detect the inhibitory effect of parkin on p53 in the PD model, parkin-transfected SH-SY5Y cells were treated with 1-methyl-4-phenylpyridinium (MPP+). The results showed that parkin could inhibit the expression of p53 protein under physiological conditions, but in the PD cell model, the function of parkin impaired, which reduced the inhibitory function of p53.

Parkin, p53, Parkinson's Disease

1. Hornykiewicz, O., Biochemical aspects of Parkinson's disease. Neurology, 1998. 51(2 Suppl 2): p. S2-9.
2. Song, N., et al., Assessments of plasma ghrelin levels in the early stages of parkinson's disease. Mov Disord, 2017. 32(10): p. 1487-1491.
3. Thomas, M. and J. Jankovic, Neurodegenerative disease and iron storage in the brain. Curr Opin Neurol, 2004. 17(4): p. 437-42.
4. Kitada, T., et al., Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature, 1998. 392(6676): p. 605-8.
5. Imai, Y., M. Soda, and R. Takahashi, Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem, 2000. 275(46): p. 35661-4.
6. Zhang, Y., et al., Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A, 2000. 97(24): p. 13354-9.
7. Alves da Costa, C. and F. Checler, Apoptosis in Parkinson's disease: is p53 the missing link between genetic and sporadic Parkinsonism? Cell Signal, 2011. 23(6): p. 963-8.
8. da Costa, C.A., et al., Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. Nat Cell Biol, 2009. 11(11): p. 1370-5.
9. Vercammen, L., et al., Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol Ther, 2006. 14(5): p. 716-23.
10. Kruse, J.P. and W. Gu, Modes of p53 regulation. Cell, 2009. 137(4): p. 609-22.
11. Brady, C.A. and L.D. Attardi, p53 at a glance. J Cell Sci, 2010. 123(Pt 15): p. 2527-32.
12. Erekat, N.S., Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease. Anat Rec (Hoboken), 2015. 298(8): p. 1472-8.
13. Vousden, K.H. and C. Prives, Blinded by the Light: The Growing Complexity of p53. Cell, 2009. 137(3): p. 413-31.
14. Levine, A.J., W. Hu, and Z. Feng, The P53 pathway: what questions remain to be explored? Cell Death Differ, 2006. 13(6): p. 1027-36.
15. Nair, V.D., et al., p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition. J Biol Chem, 2006. 281(51): p. 39550-60.
16. Mogi, M., et al., p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain. Neurosci Lett, 2007. 414(1): p. 94-7.
17. Lee, S.J., et al., Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J Biol Chem, 2006. 281(4): p. 2215-24.
18. Martin, L.J., et al., Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci, 2006. 26(1): p. 41-50