DOI QR코드

DOI QR Code

Proteomic analysis reveals that the protective effects of ginsenoside Rb1 are associated with the actin cytoskeleton in β-amyloid-treated neuronal cells

  • Hwang, Ji Yeon (Department of Physiology, School of Medicine, Kyung Hee University) ;
  • Shim, Ji Seon (Department of Physiology, School of Medicine, Kyung Hee University) ;
  • Song, Min-Young (Department of Physiology, School of Medicine, Kyung Hee University) ;
  • Yim, Sung-Vin (Department of Clinical Pharmacology, School of Medicine, Kyung Hee University) ;
  • Lee, Seung Eun (Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science) ;
  • Park, Kang-Sik (Department of Physiology, School of Medicine, Kyung Hee University)
  • Received : 2015.08.28
  • Accepted : 2015.09.22
  • Published : 2016.07.15

Abstract

Background: The ginsenoside Rb1 (Rb1) is the most abundant compound in the root of Panax ginseng. Recent studies have shown that Rb1 has a neuroprotective effect. However, the mechanisms underlying this effect are still unknown. Methods: We used stable isotope labeling with amino acids in cell culture, combined with quantitative mass spectrometry, to explore a potential protective mechanism of Rb1 in ${\beta}$-amyloid-treated neuronal cells. Results: A total of 1,231 proteins were commonly identified from three replicate experiments. Among these, 40 proteins were significantly changed in response to Rb1 pretreatment in ${\beta}$-amyloid-treated neuronal cells. Analysis of the functional enrichments and protein interactions of altered proteins revealed that actin cytoskeleton proteins might be linked to the regulatory mechanisms of Rb1. The CAP1, CAPZB, TOMM40, and DSTN proteins showed potential as molecular target proteins for the functional contribution of Rb1 in Alzheimer's disease (AD). Conclusion: Our proteomic data may provide new insights into the protective mechanisms of Rb1 in AD.

Keywords

References

  1. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci 2006;100:175-86. https://doi.org/10.1254/jphs.CRJ05010X
  2. Lee ST, Chu K, Sim JY, Heo JH, Kim M. Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord 2008;22:222-6. https://doi.org/10.1097/WAD.0b013e31816c92e6
  3. Van Kampen JM, Baranowski DB, Shaw CA, Kay DG. Panax ginseng is neuroprotective in a novel progressive model of Parkinson's disease. Exp Gerontol 2014;50:95-105. https://doi.org/10.1016/j.exger.2013.11.012
  4. Liu CX, Xiao PG. Recent advances on ginseng research in China. J Ethnopharmacol 1992;36:27-38. https://doi.org/10.1016/0378-8741(92)90057-X
  5. Liao B, Newmark H, Zhou R. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol 2002;173:224-34. https://doi.org/10.1006/exnr.2001.7841
  6. Yoshikawa T, Akiyoshi Y, Susumu T, Tokado H, Fukuzaki K, Nagata R, Samukawa K, Iwao H, Kito G. Ginsenoside Rb1 reduces neurodegeneration in the peri-infarct area of a thromboembolic stroke model in non-human primates. J Pharmacol Sci 2008;107:32-40. https://doi.org/10.1254/jphs.FP0071297
  7. Lim JH, Wen TC, Matsuda S, Tanaka J, Maeda N, Peng H, Aburaya J, Ishihara K, Sakanaka M. Protection of ischemic hippocampal neurons by ginsenoside $Rb_{1}$, a main ingredient of ginseng root. Neurosci Res 1997;28:191-200. https://doi.org/10.1016/S0168-0102(97)00041-2
  8. Wang Y, Feng Y, Fu Q, Li L. Panax notoginsenoside Rb1 ameliorates Alzheimer's disease by upregulating brain-derived neurotrophic factor and downregulating Tau protein expression. Exp Ther Med 2013;6:826-30. https://doi.org/10.3892/etm.2013.1215
  9. Xie X, Wang HT, Li CL, Gao XH, Ding JL, Zhao HH, Lu YL. Ginsenoside Rb1 protects PC12 cells against beta-amyloid-induced cell injury. Mol Med Rep 2010;3:635-9.
  10. Qian YH, Han H, Hu XD, Shi LL. Protective effect of ginsenoside Rb1 on beta-amyloid protein(1-42)-induced neurotoxicity in cortical neurons. Neurol Res 2009;31:663-7. https://doi.org/10.1179/174313209X385572
  11. Wang Y, Liu J, Zhang Z, Bi P, Qi Z, Zhang C. Anti-neuroinflammation effect of ginsenoside Rbl in a rat model of Alzheimer disease. Neurosci Lett 2011;487:70-2. https://doi.org/10.1016/j.neulet.2010.09.076
  12. Han G, Sun J, Wang J, Bai Z, Song F, Lei H. Genomics in neurological disorders. Genomics Proteomics Bioinformatics 2014;12:156-63. https://doi.org/10.1016/j.gpb.2014.07.002
  13. Sowell RA, Owen JB, Butterfield DA. Proteomics in animal models of Alzheimer's and Parkinson's diseases. Ageing Res Rev 2009;8:1-17. https://doi.org/10.1016/j.arr.2008.07.003
  14. Sultana R, Butterfield DA. Redox proteomics studies of in vivo amyloid betapeptide animal models of Alzheimer's disease: insight into the role of oxidative stress. Proteomics Clin Appl 2008;2:685-96. https://doi.org/10.1002/prca.200780024
  15. Swomley AM, Forster S, Keeney JT, Triplett J, Zhang Z, Sultana R, Butterfield DA. Abeta, oxidative stress in Alzheimer disease: evidence based on proteomics studies. Biochim Biophys Acta 2014;1842:1248-57. https://doi.org/10.1016/j.bbadis.2013.09.015
  16. Lee SY, Kim GT, Roh SH, Song JS, Kim HJ, Hong SS, Kwon SW, Park JH. Proteomic analysis of the anti-cancer effect of 20S-ginsenoside Rg3 in human colon cancer cell lines. Biosci Biotechnol Biochem 2009;73:811-6. https://doi.org/10.1271/bbb.80637
  17. Cho WC, Yip TT, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KKM. Altered expression of serum protein in ginsenoside Re-treated diabetic rats detected by SELDI-TOF MS. J Ethnopharmacol 2006;108:272-9. https://doi.org/10.1016/j.jep.2006.05.009
  18. Ma ZC, Gao Y, Wang YG, Tan HL, Xiao CR, Wang SQ. Ginsenoside Rg1 inhibits proliferation of vascular smooth muscle cells stimulated by tumor necrosis factor-alpha. Acta Pharmacol Sin 2006;27:1000-6. https://doi.org/10.1111/j.1745-7254.2006.00331.x
  19. Choi JW, Song MY, Park KS. Quantitative proteomic analysis reveals mitochondrial protein changes in MPP(+)-induced neuronal cells. Mol Biosyst 2014;10:1940-7. https://doi.org/10.1039/c4mb00026a
  20. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011;39:D561-8. https://doi.org/10.1093/nar/gkq973
  21. Abeti R, Abramov AY, Duchen MR. Beta-amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain 2011;134:1658-72. https://doi.org/10.1093/brain/awr104
  22. Huang DW, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler RW, Lane HC, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res 2007;35:W169-75. https://doi.org/10.1093/nar/gkm415
  23. McMurray CT. Neurodegeneration: diseases of the cytoskeleton? Cell Death Differ 2000;7:861-5. https://doi.org/10.1038/sj.cdd.4400764
  24. Li H, Zhu YH, Chi C, Wu HW, Guo J. Role of cytoskeleton in axonal regeneration after neurodegenerative diseases and CNS injury. Rev Neurosci 2014;25:527-42.
  25. Penzes P, Vanleeuwen JE. Impaired regulation of synaptic actin cytoskeleton in Alzheimer's disease. Brain Res Rev 2011;67:184-92. https://doi.org/10.1016/j.brainresrev.2011.01.003
  26. Kao PF, Davis DA, Banigan MG, Vanderburg CR, Seshadri S, Delalle I. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease. PLoS One 2010;5:e13337. https://doi.org/10.1371/journal.pone.0013337
  27. Zhang H, Ghai P, Wu H, Wang C, Field J, Zhou GL. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. J Biol Chem 2013;288:20966-77. https://doi.org/10.1074/jbc.M113.484535
  28. Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T, Hiraoka N, Ohta T, Ohki M, Hirohashi S. Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest 2009;89:425-32. https://doi.org/10.1038/labinvest.2009.5
  29. He J, Whelan SA, Lu M, Shen D, Chung DU, Saxton RE, Faull KF, Whitelegge JP, Chang HR. Proteomic-based biosignatures in breast cancer classification and prediction of therapeutic response. Int J Proteomics 2011;2011:896476.
  30. Moriyama K, Yahara I. Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J Cell Sci 2002;115:1591-601.
  31. Zhu X, Yao L, Guo A, Li A, Sun H, Wang N, Liu H, Duan Z, Cao J. CAP1 was associated with actin and involved in Schwann cell differentiation and motility after sciatic nerve injury. J Mol Histol 2014;45:337-48. https://doi.org/10.1007/s10735-013-9554-z
  32. Mitake S, Ojika K, Hirano A. Hirano bodies and Alzheimer's disease. Kaohsiung J Med Sci 1997;13:10-8.
  33. Delalle I, Pfleger CM, Buff E, Lueras P, Hariharan IK. Mutations in the Drosophila orthologs of the F-actin capping protein alpha- and beta-subunits cause actin accumulation and subsequent retinal degeneration. Genetics 2005;171:1757-65. https://doi.org/10.1534/genetics.105.049213
  34. Davis DA, Wilson MH, Giraud J, Xie Z, Tseng HC, England C, Herscovitz H, Tsai LH, Delalle I. Capzb2 interacts with beta-tubulin to regulate growth cone morphology and neurite outgrowth. PLoS Biol 2009;7:e1000208. https://doi.org/10.1371/journal.pbio.1000208
  35. Tian L, Liao MF, Zhang L, Lu QS, Jing ZP. A study of the expression and interaction of Destrin, cofilin, and LIMK in Debakey I type thoracic aortic dissection tissue. Scand J Clin Lab Invest 2010;70:523-8. https://doi.org/10.3109/00365513.2010.521572
  36. Klose T, Abiatari I, Samkharadze T, De Oliveira T, Jager C, Kiladze M, Valkovska N, Friess H, Michalski CW, Kleeff J. The actin binding protein destrin is associated with growth and perineural invasion of pancreatic cancer. Pancreatology 2012;12:350-7. https://doi.org/10.1016/j.pan.2012.05.012
  37. Barone E, Mosser S, Fraering PC. Inactivation of brain Cofilin-1 by age, Alzheimer's disease and gamma-secretase. Biochim Biophys Acta 2014;1842:2500-9. https://doi.org/10.1016/j.bbadis.2014.10.004
  38. Elias-Sonnenschein LS, Helisalmi S, Natunen T, Hall A, Paajanen T, Herukka SK, Laitinen M, Remes AM, Koivisto AM, Mattila KM, et al. Genetic loci associated with Alzheimer's disease and cerebrospinal fluid biomarkers in a Finnish casecontrol cohort. PLoS One 2013;8:e59676. https://doi.org/10.1371/journal.pone.0059676
  39. Chong MS, Goh LK, Lim WS, Chan M, Tay L, Chen G, Feng L, Ng TP, Tan CH, Lee TS. Gene expression profiling of peripheral blood leukocytes shows consistent longitudinal downregulation of TOMM40 and upregulation of KIR2DL5A, PLOD1, and SLC2A8 among fast progressors in early Alzheimer's disease. J Alzheimers Dis 2013;34:399-405. https://doi.org/10.3233/JAD-121621
  40. Chen X, Huang T, Zhang J, Song J, Chen L, Zhu Y. Involvement of calpain and p25 of CDK5 pathway in ginsenoside Rb1's attenuation of beta-amyloid peptide25-35-induced tau hyperphosphorylation in cortical neurons. Brain Res 2008;1200:99-106. https://doi.org/10.1016/j.brainres.2007.12.029

Cited by

  1. Attenuation of TNF-α-Induced Inflammatory Injury in Endothelial Cells by Ginsenoside Rb1 via Inhibiting NF-κB, JNK and p38 Signaling Pathways vol.8, pp.None, 2016, https://doi.org/10.3389/fphar.2017.00464
  2. Proteomic Analysis of Amyloid Corneal Aggregates from TGFBI-H626R Lattice Corneal Dystrophy Patient Implicates Serine-Protease HTRA1 in Mutation-Specific Pathogenesis of TGFBIp vol.16, pp.8, 2016, https://doi.org/10.1021/acs.jproteome.7b00188
  3. Adenylyl cyclase-associated protein 1: Structure, regulation, and participation in cellular processes vol.83, pp.1, 2018, https://doi.org/10.1134/s0006297918010066
  4. Panax ginseng components and the pathogenesis of Alzheimer's disease vol.19, pp.4, 2016, https://doi.org/10.3892/mmr.2019.9972
  5. Neuroprotective Effects of Ginseng Phytochemicals: Recent Perspectives vol.24, pp.16, 2016, https://doi.org/10.3390/molecules24162939
  6. Black Ginseng and Ginsenoside Rb1 Promote Browning by Inducing UCP1 Expression in 3T3-L1 and Primary White Adipocytes vol.11, pp.11, 2016, https://doi.org/10.3390/nu11112747
  7. Enhanced Neuroprotective Effects of Panax Ginseng G115® and Ginkgo Biloba GK501® Combinations In Vitro Models of Excitotoxicity vol.20, pp.23, 2019, https://doi.org/10.3390/ijms20235872
  8. Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/6565396