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The role and mechanism of MST1 in Parkinson's cell model

Published on Jun. 30, 2023Total Views: 640 times Total Downloads: 218 times Download Mobile

Author: Jun ZHANG 1 Yong-Le LI 1 Jie LIU 2

Affiliation: 1. Department of Neurology, The Second People's Hospital of Jingmen, Jingmen 448000, Hubei Province, China 2. Department of Pathology, The Second People's Hospital of Jingmen, Jingmen 448000, Hubei Province, China

Keywords: MST1 ULK1 S6K1 Dopaminergic neurons Parkinson's disease

DOI: 10.19960/j.issn.1005-0698.202306007

Reference: Jun ZHANG, Yong-Le LI, Jie LIU.The role and mechanism of MST1 in Parkinson's cell model[J].Yaowu Liuxingbingxue Zazhi,2023, 32(6): 655-661.DOI: 10.19960/j.issn.1005-0698.202306007.[Article in Chinese]

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Abstract

Objective  To investigate the effect of silencing MST1 gene on dopaminergic neurons in Parkinson's disease.

Method  PC12 cells were cultured and induced to differ-entiate into neurons. The neurons were divided into control group, MPP+ group, MST1 SiRNA+MPP+ group and MST1 SiRNA group. After transfection for 48 h, Western blot was used to detect the influence of MST1, ULK1 and S6K1 protein expression. Cell proliferation was detected by thiazole blue assay (MTT). The contents of MDA, SOD, GSH and CAT in cells were detected by the kit.

Results  After transfection and cultivation for 48 hours, the expression of MST1 protein in neurons of the MST1 SiRNA group was significantly reduced (P<0.001). Compared with the control group, MPP+ treatment could significantly inhibit the proliferation of PC12 cells (P<0.01), increase the activity of MDA , decrease the ac-tivity of SOD, GSH and CAT (P<0.01), increase the expression of MST1 and ULK1 proteins and decrease the expression of p-S6K1 protein (P<0.01). Compared with the MPP+ group, MST1 SiRNA transfection could effectively improve the inhibitory effect of MPP+ on PC12 cell proliferation (P<0.05), while decreasing the activity of MDA, increasing the activity of SOD, GSH and CAT (P<0.01), decreasing the protein expression of MST1 and ULK1, and increasing the protein expression of p-S6K1 (P<0.05 or P<0.01).

Conclusion  Silencing MST1 gene can inhibit oxidative stress, promote cell proliferation and play a protective role in neurons.

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References

1.Simon DK, Tanner CM, Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology[J]. Clin Geriatr Med, 2020, 36(1): 1-12. DOI: 10.1016/j.cger.2019.08.002.

2.Dirkx MF, Bologna M. The pathophysiology of Parkinson's disease tremor[J]. J Neurol Sci, 2022, 435: 120196. DOI: 10.1016/j.jns.2022.120196 .

3.李颖, 吴玉波. 多巴胺毒性代谢产物对前成骨细胞的增殖、分化、矿化及凋亡的影响[J]. 中国药师, 2021, 24(12): 2182-2187. [Li Y, Wu YB. Effects of dopamine toxic metabolites on the proliferation, differentiation, mineralization and apoptosis of pre-osteoblasts[J]. China Pharmacist, 2021, 24(12): 2182-2187.] DOI: 10.19962/j.cnki.issn1008-049X.2021.12.008

4.肖琪, 樊慧杰, 李艳荣, 等. 帕金森病发病机制研究进展[J/OL]. 解放军医学杂志: 1-15. [2023-02-24]. [Xiao Q, Fan HJ, Li YR, et al. Advances in the pathogenesis of Parkinson's disease [J/OL]. PLA Medical Journal: 1-15. [2023-02-24].] http://kns.cnki.net/kcms/detail/11.1056.R.20230223.0945.002.html.

5.Song X, Yuan B, Zhao S, et al. Effect of taurine on the proliferation, apoptosis and MST1/Hippo signaling in prostate cancer cells[J]. Transl Cancer Res, 2022, 11(6): 1705-1712. DOI: 10.21037/tcr-22-1297.

6.Ouyang H, Zhou E, Wang H. Mst1-Hippo pathway triggers breast cancer apoptosis via inducing mito-chondrial fragmentation in a manner dependent on JNK-Drp1 axis[J]. Onco Targets Ther, 2019, 12: 1147-1159. DOI: 10.2147/OTT.S193787.

7.Song H, Wang M, Xin T. Mst1 contributes to nasal epithelium inflammation via augmenting oxidative stress and mito-chondrial dysfunction in a manner dependent on Nrf2 inhibition[J]. J Cell Physiol, 2019, 234(12): 23774-23784. DOI: 10.1002/jcp.28945.

8.Wang Y, Yang Q, Shen S, et al. Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes[J]. Aging (Albany NY), 2020, 12(16): 16211-16223. DOI: 10.18632/aging.103643.

9.Sanphui P, Biswas SC. FoxO3a is activated and executes neuron death via Bim in response to β-amyloid[J]. Cell Death Dis, 2013, 4(5): e625. DOI: 10.1038/cddis.2013.148.

10.Pringsheim T, Jette N, Frolkis A, et al. The prevalence of Parkinson's disease: a systematic review and meta-analysis[J]. Mov Disord, 2014, 29: 1583-1590. DOI: 10.1002/mds.25945.

11.Kung HC, Lin KJ, Kung CT, et al. Oxidative stress, mitochondrial dysfunction, and neuroprotection of polyphenols with respect to resveratrol in parkinson's disease[J]. Biomedicines, 2021, 9(8): 918. DOI: 10.3390/biomedicines9080918.

12.Wang H, Shang Y, Wang E, et al. MST1 mediates neuronal loss and cognitive deficits: a novel thera-peutic target for Alzheimer's disease[J]. Prog Neurobiol, 2022, 214: 102280. DOI: 10.1016/j.pneurobio.2022.102280.

13.Aleksandrova K, Koelman L, Rodrigues CE. Dietary patterns and biomarkers of oxidative stress and inflammation: a systematic review of observational and intervention studies[J]. Redox Biol, 2021, 42: 101869. DOI: 10.1016/j.redox.2021.101869.

14.He B, Chen D, Zhang X, et al. Oxidative stress and ginsenosides: an update on the molecular mecha-nisms[J]. Oxid Med Cell Longev, 2022, 2022: 9299574. DOI: 10.1155/2022/9299574.

15.Sheikhpour E, Mard SA, Farbood Y, et al. The effects of gallic acid and vagotomy on motor function, intestinal transit, brain electrophysiology and oxidative stress alterations in a rat model of Parkinson's disease induced by rotenone[J]. Life Sci, 2023, 315: 121356. DOI: 10.1016/j.lfs.2022.121356.

16.谭琳娜, 谭玉勇, 鲁嘉熙, 等. ULK1蛋白激酶通过自噬及非自噬途径介导的生理、病理和疾病研究进展[J]. 生命科学研究, 2019, 23(3): 245-252. [Tan LN, Tan YY, Lu JX, et al. Advances of ULK1 functions in human physio-logical, pathological and disease processes via autophagy and non-autophagy pathways[J]. Life Sci-ence Research, 2019, 23(3): 245-252.] DOI: 10.16605/j.cnki.1007-7847.2019.03.011.

17.Qin Y, Huang J, Zhao X, et al. MiR-135a-5p and Mst1 regulate MPP + -1 induced apoptosis and au-tophagy in Parkinson's disease model in vitro[J]. Cell Signal, 2022, 94: 110328. DOI: 10.1016/j.cellsig.2022.110328.

18.Ahmed AR, Owens RJ, Stubbs CD, et al. Direct imaging of the recruitment and phosphorylation of S6K1 in the mTORC1 pathway in living cells[J]. Sci Rep, 2019, 9(1): 3408. DOI: 10.1038/s41598-019-39410-z.

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