Skip to main content
Log in

Morroniside Prevents Peroxide-induced Apoptosis by Induction of Endogenous Glutathione in Human Neuroblastoma Cells

  • Original Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

(1) Morroniside belongs to an extensive group of natural iridorid glycosides. In the present study, using human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on H2O2-mediated cytoxicity. (2) Incubation of cells with morroniside led to a significant dose-dependent elevation of cellular GSH accompanied by a marked protection against H2O2-mediated toxicity. Morroniside at 1–100 μM inhibited the formation of ROS and the activation of caspase-3 and 9, and the upregulation of Bcl-2, whereas no significant change occurred in Bax levels. (3) The results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against H2O2-induced cytotoxicity. (4) This study suggested that intracellular GSH appeared to be an important factor in morroniside-mediated cytoprotection against H2O2-toxicity in SH-SY5Y cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Ambrosio S, Espino A, Cutillas B, Bartrons R (1996) MPP+ toxicity in rat striatal slices: relationship between non-selective effects and free radical production. Neurochem Res 21:73–78

    Article  PubMed  CAS  Google Scholar 

  • Andres D, Cascales M (2002) Novel mechanism of Vitamin E protection against cyclosporine A cytotoxicity in cultured rat hepatocytes. Biochem Pharmacol 64:267–276

    Article  PubMed  CAS  Google Scholar 

  • Andres M, Jose MC, Daniel F, Manuel JD, Jorge S, Herminia D, Maria JN, Carlos JP (2001) Natural antioxidants from residual sources. Food Chem. 72:146–171

    Google Scholar 

  • Behl C (1999) Alzheimer’s disease and oxidative stress: implications for novel therapeutic approaches. Prog Neurobiol 57:301–323

    Article  PubMed  CAS  Google Scholar 

  • Bharat S, Cochran BC, Hsu M, Liu J, Ames BN, Andersen JK (2002) Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson’s disease therapy. Neurotoxicology 23:479–486

    Article  PubMed  CAS  Google Scholar 

  • Bielder JL, Roffler-Tarlov S, Schachner M, Freedman LS (1978) Mutiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38:3751–3757

    Google Scholar 

  • Chen RW, Chuang DM (1999) Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity. J Biol Chem 274:6039–6042

    Article  PubMed  CAS  Google Scholar 

  • Cole GM, Wu K, Timiras P (1985) A culture model for age-related human neurofibrillary pathology. Int J Dev Neurosci 3:23–32

    Article  CAS  Google Scholar 

  • Cutillas B, Espejo M, Ambrosio S (1998) 7-Nitroindazole prevents dopamine depletion caused by low concentrations of MPP+ in rat striatal slices. Neurochem Int 33:35–40

    Article  PubMed  CAS  Google Scholar 

  • Daniela U, Laura P, Anna C, Daniele B, Pier LC, Maurizio M (2002) Pergolide protects SH-SY5Y cell against neurodegeneration induced by H2O2. Eur J Pharmacol 434:17–20

    Article  Google Scholar 

  • Das NP, Pereira TA (1990) Effects of flavonoids on thermal autoxidation of palm oil structure-activity relationships. J Am Oil Chemists’ Soc 67:255–258

    Article  CAS  Google Scholar 

  • Deng GM, Su JH, Ivins KJ, Van Houten V, Cotman CW (1999) Bcl-2 facilitates recovery from DNA damage after oxidative stress. Exper Neurol 159:309–318

    Article  CAS  Google Scholar 

  • Duan S, Weng XC, Dong XW (1998) Antioxidant properties of butylated hydroxytoluene refluxed in ferric chloride solution. Food Chem 61:101–105

    Article  CAS  Google Scholar 

  • Farooqui SM (1994) Induction of adenylate cyclase sensitive dopamine D2-receptors in retinoic acid induced differentiated human neuroblastoma SH-SY5Y cells. Life Sci 55:1887–1893

    Article  PubMed  CAS  Google Scholar 

  • Fiers W, Beyaert R, Declercq W, Vandenabeele P (1999) More than one way to die: apoptosis and necrosis and reactive oxygen damage. Oncogene 18:7719–7730

    Article  PubMed  CAS  Google Scholar 

  • He Y, Imam SZ, Dong Z, Jankovic J, Ali SF, Appel SH, Le W (2003) Role of nitric oxide in rotenone-induced nigro-striatal injury. J Neurochem 86:1338–1345

    Article  PubMed  CAS  Google Scholar 

  • Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226

    Article  PubMed  CAS  Google Scholar 

  • Hou Q, Cymbalyuk E, Hsu SC, Xu M, Hsu YT (2003) Apoptosis modulatory activities of transiently expressed Bcl-2: roles in cytochrome C release and Bax regulation. Apoptosis 8:617–629

    Article  PubMed  CAS  Google Scholar 

  • Itano Y, Nomura Y (1995) 1-Methyl-4-phenylpyridinium ion (MPP+) causes DNA fragmentation and increases the Bcl-2 expression in human neuroblastoma, SH-SY5Y cells, through different mechanisms. Brain Res 704:240–245

    Article  PubMed  CAS  Google Scholar 

  • Jang JH, Surh YJ (2001) Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutation Res 496:181–190

    PubMed  CAS  Google Scholar 

  • Kaneko T, Baba N, Matsuo M (2003) Protection of coumarins against linoleic acid hydroperoxide-induced cytotoxicity. Chem Biol Interact 142:239–254

    Article  PubMed  CAS  Google Scholar 

  • Li CY, Li L, Li YH, AI HX, Zhang L (2005) Effects of extract from Cornus officinalis on nitric oxide and NF-κΒ in cortex of cerebral infarction rat model. China J Chinese Mater Med 30:1667–1671

    Google Scholar 

  • Maria ISR, Irene IP, Maria FMJ, Juana B (2005) Fraxetin prevents rotenone-induced apoptosis by induction of endogenous glutathione in human neuroblastoma cells. Neurosci Res 53:48–56

    Article  Google Scholar 

  • Molina-Jimenez MF, Sanchez-Reus MI, Benedi J (2003) Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. Eur J Pharmacol 472:81–87

    Article  PubMed  CAS  Google Scholar 

  • Molina-Jimenez MF, Sanchez-Reus MI,Andres D, Cascales M, Benedi J (2004) Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells. Brain Res 1009:9–16

    Article  PubMed  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Method 65:55–63

    Article  CAS  Google Scholar 

  • Pastorino JG, Chen ST, Tafani M, Snyder JW, Farber JL (1998) The overexpression of Bax produces cell death upon induction of the mitochondrial permeability transition. J Biol Chem 273:7770–7775

    Article  PubMed  CAS  Google Scholar 

  • Reed JC (1997) Double identity for proteins of the Bcl-2 family. Nature 387:773–776

    Article  PubMed  CAS  Google Scholar 

  • Saint-Cricq de Gaulejac N, Provost C, Vivas N (1999) Comparative study of polyphenol scavenging activities assessed by different methods. J Agric Food Chem 47:425–431

    Article  Google Scholar 

  • Sano K, Fujigaki Y, Miyaji T, Ikegaya N, Ohishi K, Yonemura K, Hishida A (2000) Role of apoptosis in uranyl acetate-induced acute renal failure and acquired resistance to uranyl acetate. Kidney Int 57:1560–1570

    Article  PubMed  CAS  Google Scholar 

  • Satoh I, Sakai N, Enokido Y, Uchiyama Y, Hatanaka H (1996) Free radical independent protection by nerve growth factor and Bcl-2 of PC12 cells from hydrogen peroxide triggered-apoptosis. J Biochem 120:540–546

    PubMed  CAS  Google Scholar 

  • Seyfried J, Soldner F, Kunz WS, Schulz JB, Klockgether T, Kovar KA, Wullner U (2000) Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. Neurochem Int 36:489–497

    Article  PubMed  CAS  Google Scholar 

  • Smaili SS, Hsu YT, Sanders KM, Russell JT, Youle RJ (2001) Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential. Cell Death Differ 8:909–920

    Article  PubMed  CAS  Google Scholar 

  • Sonee M, Sum T, Wang C, Mukherjee SK, (2004) The soy isoflavone, genistein, protects human cortical neuronal cells from oxidative stress. Neurotoxicology 25:885–891

    Article  PubMed  CAS  Google Scholar 

  • Tada-Oikawa S, Hiraku Y, Kawanishi M, Kawanishi S (2003) Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis. Life Sci 73:3277–3288

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Weng XC, Cheng DL (2000) Antioxidant activities of natural phenolic components from Dalbergia odorifera T. Chen. Food Chem 71:45–49

    Article  CAS  Google Scholar 

  • Weng XC, Wang W (2000) Antioxidant activity of compounds isolated from Salvia plebeian. Food Chem 71:489–493

    Article  CAS  Google Scholar 

  • Yang J, Cheng SQ, Ji CR, Liu YZ (2005) Isolation and structure identification of the chemical constituents from Cornus officinalis. Chinese Trad Herbal Drugs 36:1780–1782

    CAS  Google Scholar 

  • Zhang HY (1999) Theoretical methods used in elucidating activity differences of phenolic antioxidants. J Am Oil Chemists’ Soc 76:745–748

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This research was supported by the grants from the Program Foundation: Chinese “973” program foundation (2003CB517104); Beijing Natural Science Foundation, China (No: 7062031, 7050001, 7032013); Beijing Science and Technology Committee Program Foundation, China (D0204003000031, D0206001043191); Beijing Superiority Talented Man Foundation, China (No: 2004100501816); Base-Clinical Foundation of Capital Medical University, China (No: 2004JL02, 2006JL09); Key Laboratory for Neurodegenerative Disease Ministry of Education Foundation, China (No:2007).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lin Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, W., Huang, W., Li, L. et al. Morroniside Prevents Peroxide-induced Apoptosis by Induction of Endogenous Glutathione in Human Neuroblastoma Cells. Cell Mol Neurobiol 28, 293–305 (2008). https://doi.org/10.1007/s10571-007-9168-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-007-9168-7

Keywords

Navigation