Molecular and Cellular Biochemistry

, Volume 436, Issue 1–2, pp 203–213 | Cite as

Potential molecular mechanisms mediating the protective effects of tetrahydroxystilbene glucoside on MPP+-induced PC12 cell apoptosis

  • Lingling Zhang
  • Linhong Huang
  • Xiaobing Li
  • Cuicui Liu
  • Xin Sun
  • Leitao Wu
  • Tao Li
  • Hao Yang
  • Jianzong Chen
Article
  • 172 Downloads

Abstract

Our previous work demonstrated that tetrahydroxystilbene glucoside (TSG) was able to effectively attenuate 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis in PC12 cells partially via inhibiting reactive oxygen species (ROS) generation. However, the precise molecular mechanisms of TSG responsible for suppressing neuronal apoptosis have not been fully elucidated. To investigate the possible mechanism, we studied the neuroprotective effects of TSG on MPP+-induced PC12 cells apoptosis and explored the molecular mechanisms that mediated the effects of TSG. Our results showed that treatment with TSG prior to MPP+ exposure effectively attenuated the cell viability decrease in PC12 cells, reversed the cell apoptosis, and further restored the mitochondria membrane potential (MMP). In addition, TSG remarkably enhanced the anti-oxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and efficiently reduced the malondialdehyde (MDA) content in the PC12 cells. Meanwhile, TSG markedly upregulated the Bcl-2/Bax ratio, reversed release of Cytochrome c, and inhibited the activation of caspase-3 induced by MPP+. Furthermore, TSG significantly inhibited the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway, while extracellular signal-regulated protein kinases (ERK) phosphorylation was not affected. Together, these findings provide the basis for TSG clinical application as a new therapeutic strategy in the treatment of neurodegenerative diseases.

Keywords

Parkinson’s disease Tetrahydroxystilbene glucoside Neuroprotection PC12 cells Oxidative stress 

Notes

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81371411 and 81173590).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373:2055–2066CrossRefPubMedGoogle Scholar
  2. 2.
    Yacoubian TA, Standaert DG (2009) Targets for neuroprotection in Parkinson’s disease. Biochim Biophys Acta 1792:676–687CrossRefPubMedGoogle Scholar
  3. 3.
    Zhou C, Huang Y, Przedborski S (2008) Oxidative stress in Parkinson’s disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci 1147:93–104CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Halliwell B, Aruoma OI (1991) DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett 281:9–19CrossRefPubMedGoogle Scholar
  5. 5.
    Wang S, He H, Chen L, Zhang W, Zhang X, Chen J (2015) Protective effects of salidroside in the MPTP/MPP (+)-induced model of Parkinson’s disease through ROS-NO-related mitochondrion pathway. Mol Neurobiol 51:718–728CrossRefPubMedGoogle Scholar
  6. 6.
    Kuo HC, Lu CC, Shen CH, Tung SY, Hsieh MC, Lee KC, Lee LY, Chen CC, Teng CC, Huang WS, Chen TC, Lee KF (2016) Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade. J Transl Med 14:78CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Lotharius J, O’Malley KL (2000) The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity. J Biol Chem 275:38581–38588CrossRefPubMedGoogle Scholar
  8. 8.
    Cassarino DS, Parks JK, Parker WD Jr, Bennett JP Jr (1999) The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism. Biochim Biophys Acta 1453:49–62CrossRefPubMedGoogle Scholar
  9. 9.
    Rebois RV, Reynolds EE, Toll L, Howard BD (1980) Storage of dopamine and acetylcholine in granules of PC12, a clonal pheochromocytoma cell line. Biochemistry 19:1240–1248CrossRefPubMedGoogle Scholar
  10. 10.
    Bournival J, Quessy P, Martinoli MG (2009) Protective effects of resveratrol and quercetin against MPP+-induced oxidative stress act by modulating markers of apoptotic death in dopaminergic neurons. Cell Mol Neurobiol 29:1169–1180CrossRefPubMedGoogle Scholar
  11. 11.
    Maghsoudi A, Fakharzadeh S, Hafizi M, Abbasi M, Kohram F, Sardab S, Tahzibi A, Kalanaky S, Nazaran MH (2015) Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP (+) induced neurotoxicity. Apoptosis 20:298–309CrossRefPubMedGoogle Scholar
  12. 12.
    Qin R, Li X, Li G, Tao L, Li Y, Sun J, Kang X, Chen J (2011) Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/Akt pathway activation. Toxicol Lett 202:1–7CrossRefPubMedGoogle Scholar
  13. 13.
    Chan YC, Cheng FC, Wang MF (2002) Beneficial effects of different Polygonum multiflorum Thunb. extracts on memory and hippocampus morphology. J Nutr Sci Vitaminol (Tokyo) 48:491–497CrossRefGoogle Scholar
  14. 14.
    Yao S, Li Y, Kong L (2006) Preparative isolation and purification of chemical constituents from the root of Polygonum multiflorum by high-speed counter-current chromatography. J Chromatogr A 1115:64–71CrossRefPubMedGoogle Scholar
  15. 15.
    Li X, Li Y, Chen J, Sun J, Li X, Sun X, Kang X (2010) Tetrahydroxystilbene glucoside attenuates MPP+-induced apoptosis in PC12 cells by inhibiting ROS generation and modulating JNK activation. Neurosci Lett 483:1–5CrossRefPubMedGoogle Scholar
  16. 16.
    Zhang YZ, Shen JF, Xu JY, Xiao JH, Wang JL (2007) Inhibitory effects of 2,3,5,4′-tetrahydroxystilbene-2-O-beta-d-glucoside on experimental inflammation and cyclooxygenase 2 activity. J Asian Nat Prod Res 9:355–363CrossRefPubMedGoogle Scholar
  17. 17.
    Zhou X, Yang Q, Xie Y, Sun J, Hu J, Qiu P, Cao W, Wang S (2015) Tetrahydroxystilbene glucoside extends mouse life span via upregulating neural klotho and downregulating neural insulin or insulin-like growth factor 1. Neurobiol Aging 36:1462–1470CrossRefPubMedGoogle Scholar
  18. 18.
    Wang T, Gu J, Wu PF, Wang F, Xiong Z, Yang YJ, Wu WN, Dong LD, Chen JG (2009) Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-κB pathways and inhibition of intracellular ROS/RNS generation. Free Radic Biol Med 47:229–240CrossRefPubMedGoogle Scholar
  19. 19.
    Song F, Zhao J, Hua F, Nian L, Zhou XX, Yang Q, Xie YH, Tang HF, Sun JY, Wang SW (2015) Proliferation of rat cardiac stem cells is induced by 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-d-glucoside in vitro. Life Sci 132:68–76CrossRefPubMedGoogle Scholar
  20. 20.
    Sun FL, Zhang L, Zhang RY, Li L (2011) Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity. Eur J Pharmacol 660:283–290CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang L, Huang L, Chen L, Hao D, Chen J (2013) Neuroprotection by tetrahydroxystilbene glucoside in the MPTP mouse model of Parkinson’s disease. Toxicol Lett 222:155–163CrossRefPubMedGoogle Scholar
  22. 22.
    He H, Wang S, Tian J, Chen L, Zhang W, Zhao J, Tang H, Zhang X, Chen J (2015) Protective effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside in the MPTP-induced mouse model of Parkinson’s disease: involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways. Eur J Pharmacol 767:175–182CrossRefPubMedGoogle Scholar
  23. 23.
    Yang YW, Wu CA, Morrow WJ (2004) The apoptotic and necrotic effects of tomatine adjuvant. Vaccine 22:2316–2327CrossRefPubMedGoogle Scholar
  24. 24.
    Hu XL, Niu YX, Zhang Q, Tian X, Gao LY, Guo LP, Meng WH, Zhao QC (2015) Neuroprotective effects of Kukoamine B against hydrogen peroxide-induced apoptosis and potential mechanisms in SH-SY5Y cells. Environ Toxicol Pharmacol 40:230–240CrossRefPubMedGoogle Scholar
  25. 25.
    Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M (1983) Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol 130:1910–1917PubMedGoogle Scholar
  26. 26.
    Zamzami N, Kroemer G (2004) Methods to measure membrane potential and permeability transition in the mitochondria during apoptosis. Methods Mol Biol 282:103–115PubMedGoogle Scholar
  27. 27.
    Mignotte B, Vayssiere JL (1998) Mitochondria and apoptosis. Eur J Biochem 252:1–15CrossRefPubMedGoogle Scholar
  28. 28.
    Hengartner MO (2000) The biochemistry of apoptosis. Nature 407:770–776CrossRefPubMedGoogle Scholar
  29. 29.
    Toulouse A, Sullivan AM (2008) Progress in Parkinson’s disease—where do we stand? Prog Neurobiol 85:376–392CrossRefPubMedGoogle Scholar
  30. 30.
    Chen LW, Wang YQ, Wei LC, Shi M, Chan YS (2007) Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson’s disease. CNS Neurol Disord Drug Targets 6:273–281CrossRefPubMedGoogle Scholar
  31. 31.
    Heng Y, Zhang QS, Mu Z, Hu JF, Yuan YH, Chen NH (2016) Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra. Toxicol Lett 243:7–21CrossRefPubMedGoogle Scholar
  32. 32.
    Kumar H, Lim HW, More SV, Kim BW, Koppula S, Kim IS, Choi DK (2012) The role of free radicals in the aging brain and Parkinson’s disease: convergence and parallelism. Int J Mol Sci 13:10478–10504CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163CrossRefPubMedGoogle Scholar
  34. 34.
    Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson’s disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038–3062CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Ola MS, Nawaz M, Ahsan H (2011) Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351:41–58CrossRefPubMedGoogle Scholar
  36. 36.
    Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, Evan GI, Agid Y, Hirsch EC (2000) Caspase-3: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson’s disease. Proc Natl Acad Sci USA 97:2875–2880CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Eguchi M, Monden K, Miwa N (2003) Role of MAPK phosphorylation in cytoprotection by pro-vitamin C against oxidative stress-induced injuries in cultured cardiomyoblasts and perfused rat heart. J Cell Biochem 90:219–226CrossRefPubMedGoogle Scholar
  38. 38.
    Chang L, Karin M (2001) Mammalian MAP kinase signaling cascades. Nature 410:37–40CrossRefPubMedGoogle Scholar
  39. 39.
    Irving EA, Bamford M (2002) Role of mitogen- and stress-activated kinases in ischemic injury. J Cereb Blood Flow Metab 22:631–647CrossRefPubMedGoogle Scholar
  40. 40.
    Zhu X, Lee HG, Raina AK, Perry G, Smith MA (2002) The role of mitogen-activated protein kinase pathways in Alzheimer’s disease. Neurosignals 11:270–281CrossRefPubMedGoogle Scholar
  41. 41.
    Zhai A, Zhu X, Wang X, Chen R, Wang H (2013) Secalonic acid A protects dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced cell death via the mitochondrial apoptotic pathway. Eur J Pharmacol 713:58–67CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Lingling Zhang
    • 1
    • 2
  • Linhong Huang
    • 3
  • Xiaobing Li
    • 4
  • Cuicui Liu
    • 2
  • Xin Sun
    • 1
  • Leitao Wu
    • 1
  • Tao Li
    • 1
  • Hao Yang
    • 2
  • Jianzong Chen
    • 1
  1. 1.Research Center of Traditional Chinese MedicineXijing Hospital, Fourth Military Medical UniversityXi’anChina
  2. 2.Translational Medicine Center, Honghui HospitalXi’an Jiaotong UniversityXi’anChina
  3. 3.Clinical Pharmacy, Honghui HospitalXi’an Jiaotong UniversityXi’anChina
  4. 4.Department of Interventional Radiology, Tangdu HospitalFourth Military Medical UniversityXi’anChina

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