Browse > Article
http://dx.doi.org/10.4062/biomolther.2014.068

Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells  

Kim, Hee Ju (Natural Medicine Center, Korea Institute of Science and Technology)
Kim, Joonki (Natural Medicine Center, Korea Institute of Science and Technology)
Kang, Ki Sung (Natural Medicine Center, Korea Institute of Science and Technology)
Lee, Keun Taik (Gangneung-Wonju National University)
Yang, Hyun Ok (Natural Medicine Center, Korea Institute of Science and Technology)
Publication Information
Biomolecules & Therapeutics / v.22, no.4, 2014 , pp. 275-281 More about this Journal
Abstract
Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.
Keywords
Parkinson's disease; Autophagy; Chebulagic acid; 1-Methyl-4-phenylpyridinium ($MPP^+$);
Citations & Related Records
연도 인용수 순위
  • Reference
1 Weidberg, H., Shvets, E., Shpilka, T., Shimron, F., Shinder, V. and Elazar, Z. (2010) LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 29, 1792-1802.   DOI
2 Williams, T., Forsberg, L. J., Viollet, B. and Brenman, J. E. (2009) Basal autophagy induction without AMP-activated protein kinase under low glucose conditions. Autophagy 5, 1155-1165.   DOI
3 Pan, T., Kondo, S., Le, W. and Jankovic, J. (2008a) The role of autophagy- lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 131, 1969-1978.   DOI   ScienceOn
4 Pan, T., Kondo, S., Zhu, W., Xie, W., Jankovic, J. and Le, W. (2008b) Neuroprotection of rapamycin in lactacystin-induced neurodegeneration via autophagy enhancement. Neurobiol. Dis. 32, 16-25.   DOI   ScienceOn
5 Pan, T., Rawal, P., Wu, Y., Xie, W., Jankovic, J. and Le, W. (2009) Rapamycin protects against rotenone-induced apoptosis through autophagy induction. Neuroscience 164, 541-551.   DOI   ScienceOn
6 Park, J. H., Joo, H. S., Yoo, K. Y., Shin, B. N., Kim, I. H., Lee, C. H., Choi, J. H., Byun, K., Lee, B., Lim, S. S., Kim, M. J. and Won, M. H. (2011) Extract from Terminalia chebula seeds protect against experimental ischemic neuronal damage via maintaining SODs and BDNF levels. Neurochem. Res. 36, 2043-2050.   DOI   ScienceOn
7 Patschan, S., Chen, J. and Polotskaia, A. (2008) Lipid mediators of autophagy in stressinduced premature senescence of endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 294, 1119-1129.   DOI
8 Per, O. S. and Paul, B. G. (1982) 3-methyladenine: specifi c inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Nati. Acad. Sci. U.S.A. 79, 1889-1892.   DOI   ScienceOn
9 Ravikumar, B., Berger, Z., Vacher, C., O'Kane, C. J. and Rubinsztein, D. C. (2006) Rapamycin pre-treatment protects against apoptosis. Hum. Mol. Genet. 15, 1209-1216.   DOI   ScienceOn
10 Spowart, J. and Lum, J. J. (2010) Opening a new DOR to autophagy. EMBO. Rep. 11, 4-5.   DOI   ScienceOn
11 Tanida, I., Ueno, T. and Kominami, E. (2004) LC3 conjugation system in mammalian autophagy. Int. J. Biochem. Cell Biol. 36, 2503-2518.   DOI   ScienceOn
12 Underwood, B. R., Imarisio, S., Fleming, A., Rose, C., Krishna, G., Heard, P., Quick, M., Korolchuk, V. I., Renna, M., Sarkar, S., Garcia-Arencibia, M., O'Kane, C. J., Murphy, M. P. and Rubinsztein, D. C. (2010) Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease. Hum. Mol. Genet. 19, 3413-3429.   DOI   ScienceOn
13 Virmani, A., Gaetani, F., Binienda, Z., Xu, A., Duhart, H. and Ali, S. F. (2004) Role of mitochondrial dysfunction in neurotoxicity of $MPP^+$: partial protection of PC12 cells by acetyl-L-carnitine. Ann. N. Y. Acad. Sci. 1025, 267-273.   DOI   ScienceOn
14 Liang, J., Shao, S. H., Xu, Z. X., Hennessy, B., Ding, Z., Larrea, M., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., Slingerland, J. M. and Mills, G. B. (2007) The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat. Cell. Biol. 9, 218-224.   DOI   ScienceOn
15 Kabeya, Y., Mizushima, N., Yamamoto, A., Satsuki, O. O., Ohsumi, Y. and Yoshimori, T. (2004) LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell Sci. 117, 2805-2812.   DOI   ScienceOn
16 Ko, H. S., Kim, Y. J., Amor, E. C., Lee, J. W., Kim, H. C., Kim, H. J. and Yang, H. O. (2011) Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells. J. Cell. Biochem. 112, 2471-2479.   DOI   ScienceOn
17 Larsen, K. E. and Sulzer, D. (2002) Autophagy in neurons: a review. Histol. Histopathol. 17, 897-908.
18 Liu, D., Si, H., Reynolds, K. A., Zhen, W., Jia, Z. and Dillon, J. S. (2007) Dehydroepiandrosterone protects vascular endothelial cells against apoptosis through a Galphai protein-dependent activation of phosphatidylinositol 3-kinase/Akt and regulation of antiapoptotic Bcl-2 expression. Endocrinology 148, 3068-3076.   DOI   ScienceOn
19 Mathiasen, J. R., McKenna, B. A., Saporito, M. S., Ghadge, G. D., Roos, R. P., Holskin, B. P., Wu, Z. L., Trusko, S. P., Connors, T. C., Maroney, A. C., Thomas, B. A., Thomas, J. C. and Bozyczko- Coyne, D. (2004) Inhibition of mixed lineage kinase 3 attenuates $MPP^+$-induced neurotoxicity in SH-SY5Y cells. Brain Res. 1003, 86-97.   DOI   ScienceOn
20 Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E. L., Hall, D. H. and Levine, B. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387-1391.   DOI   ScienceOn
21 Bollimuntha, S., Singh, B. B. and Shavali, S. (2005) TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. J. Biol. Chem. 280, 2132-2140.   DOI
22 Nowak, J., Archange, C., Joel, T. L., Pontarotti, P., Pe'busque, M., Vaccaro, M. I., Velasco, G., Dagorn, J. C. and Iovanna, J. L. (2009) The TP53INP2 protein is required for autophagy in mammalian cells. Mol. Biol. Cell 20, 870-881.
23 Nowak, J. and Iovanna, J. L. (2009) TP53INP2 is the new guest at the table of self-eating. Autophagy 5, 383-384.   DOI
24 Bao, X. X., Xie, B. S., Li, Q., Li, X. P., Wei, L. H. and Wang, J. L. (2012) Nifedipine induced autophagy through Beclin1 and mTOR pathway in endometrial carcinoma cells. Chin. Med. J. 125, 3120-3126
25 Chang, C. L. and Lin, C. S. (2012) Phytochemical composition, antioxidant activity, and neuroprotective effect of Terminalia chebula Retzius extracts. Evid. Based Complement. Alternat. Med. 2012, 125247.
26 Chen, X. C., Fang, F., Zhu, Y. G., Chen, L. M., Zhou, Y. C. and Chen, Y. (2003) Protective effect of ginsenoside Rg1 on $MPP^+$-induced apoptosis in SH-SY5Y cells. J. Neural Transm. 110, 835-845.   DOI   ScienceOn
27 Chen, Z., Lu, T., Yue, X., Wei, N., Jiang, Y., Chen, M., Ni, G., Liu, X. and Xu, G. (2010) Neuroprotective effect of ginsenoside Rb1 on glutamate-induced neurotoicity : With emphasis on autophagy. Neurosci. Lett. 482, 264-268.   DOI   ScienceOn
28 Choi, J. Y., Jang, E. H., Park, C. S. and Kang, J. H. (2005) Enhanced susceptibility to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity in high-fat diet induced obesity. Free Radic. Biol. Med. 38, 806-816.   DOI   ScienceOn
29 Dauer, W. and Przedborski, S. (2003) Parkinson's disease: mechanisms and models. Neuron 39, 889-909 .   DOI   ScienceOn
30 Dadakhujaev, S., Noh, H. S., Jung, E. J., Cha, J. Y., Baek, S. M., Ha, J. H. and Kim, D. R. (2010) Autophagy protects the rotenone-induced cell death in alpha-synuclein overexpressing SH-SY5Y cells. Neurosci. Lett. 472, 47-52 .   DOI   ScienceOn
31 Gurusamy, N., Lekli, I., Mukherjee, S., Ray, D., Ahsan, K., Gherghiceanu, M., Popescu, L. M. and Das, D. K. (2010) Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc. Res. 86, 103-112.   DOI   ScienceOn
32 Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Ichiro, S., Okano, H. and Mizushima, N. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885-889.   DOI   ScienceOn
33 Han, J., Pan, X. Y., Xu, Y., Xiao, Y., An, Y., Tie, L., Pan, Y. and Li, X. J. (2012) Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy 8, 812-825.   DOI   ScienceOn
34 Hay, N. and Sonenberg, N. (2004) Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945.   DOI   ScienceOn
35 Baliga, M. S. and Dsouza, J. J. (2011) Amla(Emblica offi cinalis Gaertn), a wonder berry in the treatment and prevention of cancer. Eur. J. Cancer Prev. 20, 225-239.   DOI   ScienceOn
36 Bae, N. Y., Ahn, T. K., Chung, S. K., Oh, M. S., Ko, H. S., Oh, H. G., Park, G. H. and Yang, H. O. (2011) The neuroprotective effect of modified Yeoldahanso-tang via autophagy enhancement in models of Parkinson's disease. J. Ethnopharmacol. 134, 313-322.   DOI   ScienceOn
37 Wu, Y., Li, X., Zhu, J. X., Xie, W., Le, W., Fan, Z., Jankovic, J. and Pan, T. (2011) Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson's disease. Neurosignals 19, 163-174.   DOI   ScienceOn
38 Shin, H. Y., Chu, S. H., Lee, H. K. and Lee, J. W. (2011) mTOR inhibitor as a potential drug of age-related disease. Korean. J. Clin. Geri. 12, 149-159.
39 Mauvezin, C., Orpinell, M., Francis, V. A., Mansilla, F., Duran, J., Ribas, V., Palacin, M., Boya, P., Teleman, A. A. and Zorzano, A. (2010) The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells. EMBO Rep. 11, 37-44.   DOI   ScienceOn