Effects of Loganin on MPTP-Induced Autophagy in PC12 Cells

doi:10.3969/j.issn.2095-1396.2016.05.002

Abstract

Abstract: Objective：To investigate the effects of loganin on MPTP-induced autophagy in PC12 cells. Methods：The autophagy model was established on PC12 cells by neurotoxin 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（ MPTP）. The expression of autophagy-related factor microtubuleassociated protein1light chain 3-β（ LC3B） in PC12 cells was investigated at different concentrations and different time after MPTP administration. Then，the effects of loganin on the autophagy related signaling pathway induced by MPTP administration in PC12 cells were detected. Results：LC3B was significantly up-regulated at 12 h after MPTP treatment and the concentration of MPTP at 100 μg·mL-1 showed the strongest action on LC3B expression. Compared to MPTP treated group，the expression of LC3B was significantly down-regulated by loganin at dose of 200 μg·mL-1 combined with MPTP treatment. Furthermore，expression of lysosome associated membrane protein 2 （LAMP-2） was significantly downregulated by loganin at dose of 400 μg·mL-1 combined with MPTP treatment. Conclusions：MPTP at dose of 100 μg·mL-1 could induce the high expression of autophagy protein at 12 h after treatment. Loganin reduced expression of autophagosomes induced by MPTP in PC12 cells，and the inhibitory mechanism may be related to its enhancing digestion of lysosomes to autophagosomes.

Key words: MPTP, autophagy, loganin, lysosome, Parkinson&, rsquo, s disease

WANG Lin-fang，HUANG Shu-bing，XU Yi-da，CUI Chun，SHEN Yan-qin. Effects of Loganin on MPTP-Induced Autophagy in PC12 Cells[J]. Acta Neuropharmacologica, 2016, 6(5): 14-21.

References

1. Syed F Ali, Zbigniew K Binienda, Syed Z Imam. Molecular aspects of dopaminergic neurodegeneration: gene-environment interaction in parkin dysfunction [J]. Int J Environ Res Public Health, 2011, 8(12): 4702-4713.

2. Min Kong, Ba Mao-wen, Ren Chao, et al. An updated meta-analysis of amantadine for treating dyskinesia in Parkinson's disease [J]. Oncotarget, 2017, 8: 57316-57326.

3. Jerzy Leszek, George E Barreto, Kazimierz Gasiorowski, et al. Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system [J]. CNS Neurol Disord Drug Targets, 2016, 15(3): 329-336.

4. Mitesh Lotia, Joseph Jankovic. New and emerging medical therapies in Parkinson's disease [J]. Expert Opin Pharmacother, 2016, 17(7): 895-909.

5. Wang Xin, Timothy Huang, Bu Guo-jun, et al. Dysregulation of protein trafficking in neurodegeneration [J]. Mol Neurodegener, 2014, 9: 31.

6. Ana Maria Sanchez-Perez, Berta Claramonte-Clausell, Juan Vicente Sanchez-Andres, et al. Parkinson's disease and autophagy [J]. Parkinsons Dis, 2012, 2012: 429524.

7. Wang Zi-ying, Liu Jing-yi, Yang Chuan-bin, et al. Neuroprotective natural products for the treatment of Parkinson's disease by targeting the autophagy-lysosome pathway: a systematic review [J]. Phytother Res, 2017, doi: 10.1002/ptr.5834.

8. Rebecca Banerjee, M Flint Beal, Bobby Thomas. Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications [J]. Trends Neurosci, 2010, 33(12): 541-549.

9. Brian Spencer, Rewati Potkar, Margarita Trejo, et al. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases [J]. J Neurosci, 2009, 29(43): 13578-13588.

10. Md Ataur Rahman, Hyewhon Rhim. Therapeutic implication of autophagy in neurodegenerative diseases [J]. BMB Rep, 2017, 50(7): 345-354 .

11. Orit Bar-Am, Tamar Amit, Moussa B H Youdim. Aminoindan and hydroxyaminoindan, metabolites of rasagiline and ladostigil, respectively, exert neuroprotective properties in vitro [J]. J Neurochem, 2007, 103(2): 500-508.

12. Zheng Hai-lin, Shunit Gal, Lev M Weiner, et al. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition [J]. J Neurochem, 2005, 95(1): 68-78.

13. Muller-Rebstein S, Trenkwalder C, Oertel W H, et al. Pharmacotherapy of Parkinson's disease : aspects of drug safety [J]. Nervenarzt, 2017, DOI: 10.1007/s00115-017-0345-8.

14. Hemant Kumar, Sandeep Vasant More, Han Sang-don, et al. Promising therapeutics with natural bioactive compounds for improving learning and memory--a review of randomized trials [J]. Molecules, 2012, 17(9): 10503-10539.

15. Yang Jin-song, Wu Xiao-hong, Yu Hao-gang, et al. Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats [J]. Inflammopharmacology, 2017, 25(4): 471-484.

16. Ki Yong Lee, Sang Hyun Sung, Seung Hyun Kim, et al. Cognitive-enhancing activity of loganin isolated from Cornus officinalis in scopolamine-induced amnesic mice [J]. Arch Pharm Res, 2009, 32(5): 677-683.

17. Seung-Hwan Kwon, Ji-Ah Kim, Sa-ik Hong, et al. Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells [J]. Neurochem Int, 2011, 58(4): 533-541.

18. Hyeri Kim, Kumju Youn, Mok-Ryeon Ahn, et al. Neuroprotective effect of loganin against Abeta25-35-induced injury via the NF-kappaB-dependent signaling pathway in PC12 cells [J]. Food Funct, 2015, 6(4): 1108-1116.

19. Yao Li, Peng Shi-xiao, Xu Yi-da, et al. Unexpected neuroprotective effects of loganin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity and cell death in zebrafish [J]. J Cell Biochem, 2017, 118(3): 615-628.

20. Carlos Fonck, Michel Baudry. Toxic effects of MPP(+) and MPTP in PC12 cells independent of reactive oxygen species formation [J]. Brain Res, 2001, 905(1-2): 199-206.

21. Daniel J Klionsky. Autophagy: from phenomenology to molecular understanding in less than a decade [J]. Nat Rev Mol Cell Biol, 2007, 8(11): 931-937.

22. Zou Jing, Chen Zhao-yu, Wei Xiao-bo, et al. Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units [J]. Cell Death Dis, 2017, 8(6): e2854.

23. Zhang Sheng, Gui Xue-hong, Huang Li-ping, et al. Neuroprotective effects of beta-asarone against 6-hydroxy dopamine-induced parkinsonism via JNK/Bcl-2/Beclin-1 pathway [J]. Mol Neurobiol, 2016, 53(1): 83-94.

24. Yoshinobu Ichimura, Taichi Kumanomidou, Sou Yu-shin, et al. Structural basis for sorting mechanism of p62 in selective autophagy [J]. J Biol Chem, 2008, 283(33): 22847-22857.

25. Terje Johansen, Trond Lamark. Selective autophagy mediated by autophagic adapter proteins [J]. Autophagy, 2011, 7(3): 279-296.

26. Geir Bjorkoy, Trond Lamark, Andreas Brech, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death [J]. J Cell Biol, 2005, 171(4): 603-614.

27. Adolfo Garcia Erustes, Fernanda Yakel Stefani, Juliana Yoshie Terashima, et al. Overexpression of alpha-synuclein in an astrocyte cell line promotes autophagy inhibition and apoptosis [J]. J Neurosci Res, 2017.

28. Joungmok Kim, Mondira Kundu, Benoit Viollet, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 [J]. Nat Cell Biol, 2011, 13(2): 132-141.

29. Shen Yu-fei, Tang Yu, Zhang Xiao-jie, et al. Adaptive changes in autophagy after UPS impairment in Parkinson's disease [J]. Acta Pharmacol Sin, 2013, 34(5): 667-673.

30. Ana Maria Cuervo, J Fred Dice. A receptor for the selective uptake and degradation of proteins by lysosomes [J]. Science, 1996, 273(5274): 501-503.

31. Pang Shu-chao, Chen Dong-feng, Zhang Ai-mei, et al. Genetic analysis of the LAMP-2 gene promoter in patients with sporadic Parkinson's disease [J]. Neurosci Lett, 2012, 526(1): 63-67.

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