Advertisement

Cellular and Molecular Neurobiology

, Volume 36, Issue 1, pp 103–111 | Cite as

Protective Effects of Coenzyme Q10 Against Hydrogen Peroxide-Induced Oxidative Stress in PC12 Cell: The Role of Nrf2 and Antioxidant Enzymes

  • Li Li
  • Jikun Du
  • Yaru Lian
  • Yun Zhang
  • Xingren Li
  • Ying Liu
  • Liyi Zou
  • Tie Wu
Original Research

Abstract

Oxidative stress is a major component of harmful cascades activated in neurodegenerative disorders. Coenzyme Q10 (CoQ10), an essential component in the mitochondrial respiratory chain, has recently gained attention for its potential role in the treatment of neurodegenerative disease. Here, we investigated the possible protective effects of CoQ10 on H2O2-induced neurotoxicity in PC12 cells and the underlying mechanism. CoQ10 showed high free radical-scavenging activity as measured by a DPPH and TEAC. Pre-treatment of cells with CoQ10 diminished intracellular generation of ROS in response to H2O2. H2O2 decreased viability of PC12 cells which was reversed by pretreatment with CoQ10 according to MTT assay. H2O2-induced lipid peroxidation was attenuated by CoQ10 as shown by inhibition of MDA formation. Furthermore, pre-incubation of the cells with CoQ10 also restored the activity of cellular antioxidant enzymes which had been altered by H2O2. Moreover, CoQ10 induced Nrf2 nuclear translocation, the upstream of antioxidant enzymes. These findings suggest CoQ10 augments cellular antioxidant defense capacity through both intrinsic free radical-scavenging activity and activation of Nrf2 and subsequently antioxidant enzymes induction, thereby protecting the PC12 cells from H2O2-induced oxidative cytotoxicity.

Keywords

Coenzyme Q10 Antioxidant enzyme Nrf2 Neurodegeneration 

Notes

Acknowledgments

We gratefully acknowledge financial support of this work by Guangdong Medical College foundation (No. B2011011), Zhanjiang Science and Technology Planning Project (No. 2012C3104018), Shenzhen Science and Technology Planning Project (No. 201302173), Innovation Experiment Program for University Students of Guangdong Medical College (LZDM011).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Statement

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Beal MF (2003) Bioenergetic approaches for neuroprotection in Parkinson’s disease. Ann Neurol 53(3):39–47CrossRefGoogle Scholar
  2. Bhat V, Weiner WJ (2005) Parkinson’s disease. diagnosis and the initiation of therapy. Minerva Med 96:145–154PubMedGoogle Scholar
  3. Dinis TC, Maderia VM, Almeida L (1994) Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 315:161–169PubMedCrossRefGoogle Scholar
  4. Feigin A, Kieburtz K, Como P, Hickey C, Claude K, Abwender D, Zimmerman C, Steinberg K, Shoulson I (1996) Assessment of coenzyme Q10 tolerability in Huntington’s disease. Mov Disord 11:321–323PubMedCrossRefGoogle Scholar
  5. Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci 22(5):1592–1599PubMedGoogle Scholar
  6. Ferrante KL, Shefner J, Zhang H, Betensky R, O’Brien M, Yu H, Fantasia M, Taft J, Beal MF, Traynor B, Newhall K, Donofrio P, Caress J, Ashburn C, Freiberg B, O’Neill C, Paladenech C, Walker T, Pestronk A, Abrams B, Florence J, Renna R, Schierbecker J, Malkus B, Cudkowicz M (2005) Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS. Neurology 65(11):1834–1836PubMedCrossRefGoogle Scholar
  7. Gazdík F, Piják MR, Borová A, Gazdíková K (2003) Biological properties of coenzyme Q10 and its effects on immunity. Cas Lek Cesk 142(7):390–393PubMedGoogle Scholar
  8. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140(6):918–934PubMedPubMedCentralCrossRefGoogle Scholar
  9. Guroff G (1985) PC12 cells as a model of neuronal differentiation. Bottenstein JE Cell culture in neurosciences. Plemun Press, New York, pp 245–272CrossRefGoogle Scholar
  10. Itoh K, Ishii T, Wakabayashi N, Yamamoto M (1999) Regulatory mechanisms of cellular response to oxidative stress. Free Radical Res 31(4):319–324CrossRefGoogle Scholar
  11. Itoh K, Wakabayashi N, Katoh Y, Ishii T, O’Connor T, Yamamoto M (2003) Keap1 regulates both cytoplasmic–nuclearshuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8(4):379–391PubMedCrossRefGoogle Scholar
  12. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2–ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 1147:61–69PubMedPubMedCentralCrossRefGoogle Scholar
  13. Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1–Nrf2–-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116PubMedCrossRefGoogle Scholar
  14. Khandhar SM, Marks WJ (2007) Epidemiology of Parkinson’s disease. Dis Mon 53(4):200–205PubMedCrossRefGoogle Scholar
  15. LaFerla FM, Green KN, Oddo S (2007) Intracellular amyloid-beta in Alzheimer’s disease. Nat Rev Neurosci 8:499–509PubMedCrossRefGoogle Scholar
  16. Lee JM, Shih AY, Murphy TH, Johnson JA (2003) NF–E2–related factor–2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278:37948–37956PubMedCrossRefGoogle Scholar
  17. Li L, Du JK, Zou LY, Wu T, Lee YW, Kim YH (2013) Decursin isolated from Angelica gigas Nakai rescues PC12 Cells from amyloid β–protein–induced neurotoxicity through Nrf2-Mediated upregulation of heme oxygenase-1: potential roles of MAPK. Evid-Based Complement Alternate Med. doi: 10.1155/2013/467245 Google Scholar
  18. Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci USA 95(15):8892–8897PubMedPubMedCentralCrossRefGoogle Scholar
  19. Mukai FH, Goldstein BD (1976) Mutagenicity of malondialdehyde, a decomposition product of peroxidised polyunsaturated fatty acids. Science 191:868–869PubMedCrossRefGoogle Scholar
  20. Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295PubMedPubMedCentralCrossRefGoogle Scholar
  21. Pi J, Zhang Q, Woods CG, Wong V, Collins S, Andersen ME (2008) Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid. Toxicol Appl Pharmacol 226:236–243PubMedCrossRefGoogle Scholar
  22. Pratico D, Clark CM, Liun F, Rokach J, Lee VY, Trojanowski JQ (2002) Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 59(6):972–976PubMedCrossRefGoogle Scholar
  23. Reeve K, Krishnan KJ, Turnbull D (2008) Mitochondrial DNA mutations in disease, aging, and neurodegeneration. Ann N Y Acad Sci 1147:21–29PubMedCrossRefGoogle Scholar
  24. Saeidnia S, Abdollahi M (2013) Toxicological and pharmacological concerns on oxidative stress and related diseases. Toxicol Appl Pharmacol 273:442–455PubMedCrossRefGoogle Scholar
  25. Sen CK, Packer L (1996) Antioxidant and redox regulation of gene transcription. FASEB J 10:709–720PubMedGoogle Scholar
  26. Shih AY, Imbeault S, Barakauskas V, Erb H, Jiang L, Li P, Murphy TH (2005) Induction of the Nrf2–driven antioxidant response confers neuroprotection during mitochondrial stress in vivo. J Biol Chem 280(24):22925–22936PubMedCrossRefGoogle Scholar
  27. Shults CW, Haas R (2005) Clinical trials of coenzyme Q10 in neurological disorders. BioFactors 25(1–4):117–126PubMedCrossRefGoogle Scholar
  28. Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59(10):1541–1550PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Dongguan Scientific Research CenterGuangdong Medical UniversityDongguanChina
  2. 2.Department of Clinical LaboratoryShenzhen Shajing Affiliated Hospital of Guangzhou Medical UniversityShenzhenChina
  3. 3.Department of PharmacologyGuangdong Medical UniversityDongguanChina

Personalised recommendations