鱼藤酮对MN9D细胞蛋白磷酸酶2A活力的影响

doi:10.3969/j.issn.1006-9771.2018.01.007

Abstract

Abstract: Objective To study whether and how rotenone reduces the activity of protein phophatase 2A (PP2A).Methods MN9D cells (mouse midbrain dopaminergic cell line) were divided into normal group (normal cultured), control group (dimethyl sulfoxide of same volume with rotenone group was added in medium), rotenone group (50 nmol/L rotenone was added to the culture medium for 24 hours) and rotenone+C2 group (pretreatment of 5 mol/L C2-ceramide for eight hours, and then exposed to 50 nmol/L rotenone for 24 hours). MTT was used to detect cell viability. Total PP2A levels and tyrosine phosphorylation levels were measured with Western blotting. PP2A activity was detected with colorimetric assay.Results Compared with the control group, the cell viability reduced (P<0.01), phosphorylation of tyrosine 307 of PP2A inceased (P<0.01), and activity of PP2A decreased in the rotenone group (P<0.05). And compared with the rotenone group, the cell viability improved (P<0.01), phosphorylation of tyrosine 307 of PP2A deceased (P<0.01), and activity of PP2A increased (P<0.05) in the rotenone+C2 group.Conclusion Rotenone can inhibit activity of PP2A through increasing phosphorylation of tyrosine 307 at the catalytic subunit of PP2A, which might be involved in reducing cell viability, and implicate a new treatment strategy for Parkinson's disease.

Key words: Parkinson's disease, rotenone, cell viability, protein phosphatase 2A

CLC Number:

R742.5

WANG Yi, DU Ting-ting, LIU Shu-jia, LIU Jia, LU Yong-quan, YANG Hui. Influence of Rotenone on Activity of Protein Phosphates 2A in MN9D Cells[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2018, 24(1): 37-42.

References

[1] Trinh J, Farrer M. Advances in the genetics of Parkinson disease [J]. Nat Rev Neurol, 2013, 9(8): 445-454.
[2] Mercado NM, Collier TJ, Freeman T, et al. Repairing the aged Parkinsonian striatum: lessons from the lab and clinic [J]. J Clin Cell Immunol, 2016, 7(6): 476-489.
[3] Goldman SM. Environmental toxins and Parkinson's disease [J]. Annu Rev Pharmacol Toxicol, 2014, 54: 141-164.
[4] Maturana MG, Pinheiro AS, Souza TL, et al. Unveiling the role of the pesticides paraquat and rotenone on alpha-synuclein fibrillation in vitro [J]. Neurotoxicology, 2014, 46C: 35-43.
[5] Ma KL, Song LK, Long WA, et al. Deletion in exon 5 of the SNCA gene and exposure to rotenone leads to oligomerization of alpha-synuclein and toxicity to PC12 cells [J]. Brain Res Bull, 2013, 90: 127-131.
[6] Pan-Montojo FJ, Funk RH. Oral administration of rotenone using a gavage and image analysis of alpha-synuclein inclusions in the enteric nervous system [J]. J Vis Exp, 2010(44): e2123-e2127.
[7] Pan-Montojo F, Schwarz M, Winkler C, et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice [J]. Sci Rep, 2012, 2: 898-1009.
[8] Ferris CF, Marella M, Smerkers B, et al. A phenotypic model recapitulating the neuropathology of Parkinson's disease [J]. Brain Behav, 2013, 3(4): 351-366.
[9] Liu HF, Ho PW, Leung GC, et al. Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson's disease [J]. Sci Rep, 2017, 7: 40887-40901.
[10] Liu Y, Sun JD, Song LK, et al. Environment-contact administration of rotenone: A new rodent model of Parkinson's disease [J]. Behav Brain Res, 2015, 294: 149-161.
[11] Fujiwara H, Hasegawa M, Dohmae N, et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions [J]. Nat Cell Biol, 2002, 4(2): 160-164.
[12] Wang Y, Shi M, Chung KA, et al. Phosphorylated alpha-synuclein in Parkinson's disease [J]. Sci Transl Med, 2012, 4(121): 121ra20.
[13] Strack S, Westphal RS, Colbran RJ, et al. Protein serine/threonine phosphatase 1 and 2A associate with and dephosphorylate neurofilaments [J]. Brain Res Mol Brain Res, 1997, 49(1-2): 15-28.
[14] Arboleda G, Cardenas Y, Rodriguez Y, et al. Differential regulation of AKT, MAPK and GSK3beta during C2-ceramide-induced neuronal death [J]. Neurotoxicology, 2010, 31(6): 687-693.
[15] Fedida-Metula S, Feldman B, Koshelev V, et al. Lipid rafts couple store-operated Ca 2+ entry to constitutive activation of PKB/Akt in a Ca 2+ /calmodulin-, Src- and PP2A-mediated pathway and promote melanoma tumor growth [J]. Carcinogenesis, 2012,33(4): 740-750.
[16] Law B, Rossie S. The dimeric and catalytic subunit forms of protein phosphatase 2A from rat brain are stimulated by C2-ceramide [J]. J Biol Chem, 1995, 270(21): 12808-12813.
[17] Dobrowsky RT, Kamibayashi C, Mumby MC, et al. Ceramide activates heterotrimeric protein phosphatase 2A [J]. J Biol Chem, 1993, 268(21): 15523-15530.
[18] Wang Y, Liu J, Chen M, et al. The novel mechanism of rotenone-induced alpha-synuclein phosphorylation via reduced protein phosphatase 2A activity [J]. Int J Biochem Cell Biol, 2016, 75: 34-44.
[19] Paleologou KE, Schmid AW, Rospigliosi CC, et al. Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein [J]. J Biol Chem, 2008, 283(24): 16895-16905.
[20] Smith WW, Margolis RL, Li X, et al. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells [J]. J Neurosci, 2005, 25(23): 5544-5552.
[21] Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease [J]. Nat Neurosci, 2005, 8(5): 657-663.
[22] Uversky VN. Neuropathology, biochemistry, and biophysics of alpha-synuclein aggregation [J]. J Neurochem, 2007, 103(1): 17-37.
[23] Benskey MJ, Perez RG, Manfredsson FP. The contribution of alpha synuclein to neuronal survival and function–Implications for Parkinson's disease [J]. J Neurochem, 2016, 137(3): 331-359.
[24] Cannon JR, Greenamyre JT. Neurotoxic in vivo models of Parkinson's disease recent advances [J]. Prog Brain Res, 2010, 184: 17-33.
[25] Shimoyama S, Kasai S, Kahn-Perles B, et al. Dephosphorylation of Sp1 at Ser-59 by protein phosphatase 2A (PP2A) is required for induction of CYP1A1 transcription after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or omeprazole [J]. Biochim Biophys Acta, 2014, 1839(2): 107-115.
[26] Wlodarchak N, Xing Y. PP2A as a master regulator of the cell cycle [J]. Crit Rev Biochem Mol Biol, 2016, 51(3): 162-184.
[27] Liu J, Chen M, Wang X, et al. Piperine induces autophagy by enhancing protein phosphotase 2A activity in a rotenone-induced Parkinson's disease model [J]. Oncotarget, 2016, 7(38): 60823-60843.

Influence of Rotenone on Activity of Protein Phosphates 2A in MN9D Cells

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Metrics

Comments

Recommended 0

[1]	WU Jiayu, MENG Detao, LIANG Xiaoxiao. Effect of physical activity levels on risk of Parkinson's disease: a cross-sectional analysis based on China Health and Retirement Longitudinal Study [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(10): 1135-1139.
[2]	WANG Jingxuan, LÜ Diyang, FANG Boyan. Non-drug rehabilitation for gait abnormality of Parkinson's disease: a review based on ClinicalTrials.gov [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2023, 29(7): 816-821.
[3]	SHI Manxinyu,MENG Detao,FANG Boyan. Advance in Parkinson's disease rehabilitation: a visualization analysis [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(9): 1060-1064.
[4]	WANG Jieping,PENG Juan,ZHANG Feixue,FAN Bishuang,XU Fangyuan. Effect of interlimb-coordinated training on pulmonary function in patients with early primary Parkinson's disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(8): 966-971.
[5]	TAN Mingdan,FENG Dingyao,CHEN Xi,LIU Hanjun,LI Yongxue. Reliability and validity of Chinese version of Dysarthria Impact Profile for Parkinson's disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(6): 696-703.
[6]	XI Xiaoming,BI Hongyan. Effect of abdominal torsion movement on depression, constipation, motor symptoms and quality of life in patients with Parkinson's disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2022, 28(2): 220-226.
[7]	XIAO Lin-na,LI Xiao-hong. Impulse Control Disorder in Parkinson's Disease: A Scoping Review [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(7): 774-779.
[8]	MA Hui-zi,FANG Jin-ping,FENG Tao,JIANG Ying. Structural Differences of Depression for Patients with Parkinson's Disease Using Hamilton Depression Scale [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(7): 829-833.
[9]	Xin LIU,Zhi-ke YIN,Tao FENG,Yong-mei DENG,Yue-ying ZHAO,Ke DONG,Chun-xue WANG,Hui-zi MA. Risk Factors of Apathy in Parkinson's Disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(6): 719-723.
[10]	Kun-peng LI,Zong-lei ZHOU,Zi-nan ZHANG,Bo-han SHI,Hao CHEN,Yun LUO,Yan ZHU. Effects of Respiratory Training on Pulmonary Function and Motor Function for Patients with Parkinson's Disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(3): 320-324.
[11]	Ying JIANG,Jin-ping FANG,Tao FENG,Hui-zi MA. Structural Differences in Series Scores of Hamilton Anxiety Scale in Parkinson's Disease Patients [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(3): 325-328.
[12]	WANG Xiang-yu, DONG Qing, DONG Shuang-shuang, CAI Zeng-lin. Effects of Baduanjin and Balancer Exercise on Motor and Non-motor Symptoms of Parkinson's Disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(1): 111-116.
[13]	XIONG Wei,JIANG Lei,WANG Qiang,LUO Fang. Perioperative Management of Anesthesia for Patients with Parkinson's Disease (review) [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(11): 1316-1321.
[14]	SUN Wen-yu,BI Hong-yan. Effects of Daoyin on Motor Function, Balance and Quality of Life for Patients with Parkinson's Disease [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(7): 836-841.
[15]	LI Wei,GONG Wei-jun,GAO Lei,ZHEN Qiao-xia,ZHANG Qiao-rong,QIE Shu-yan,FANG Bo-yan. Rehabilitation Approaches from European Physiotherapy Guideline for Parkinson's Disease: A Comment [J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(5): 614-620.