Skip to main content

Advertisement

SpringerLink
Log in

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Brains affected by Alzheimer’s disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

Abbreviations

AD:

Alzheimer’s disease

Aβ:

β-Amyloid

ROS:

Reactive oxygen species

mtDNA:

Mitochondrial DNA

mPTP:

Mitochondrial permeability transition pores

DCFH-DA:

Dichlorofluorescin diacetate

NRFU:

Normalized relative fluorescence units

THF:

Tetrahydrofuran

BHT:

Butylated hydroxytoluene

COX I:

Cytochrome c oxidase subunit I

COX IV:

Cytochrome c oxidase subunit IV

ND6:

NADH dehydrogenase subunit 6

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  1. Zhu X, Perry G, Smith MA, Wang X (2013) Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer’s disease. J Alzheimers Dis 33(Suppl 1):S253–S262. doi:10.3233/JAD-2012-129005

    PubMed  PubMed Central  Google Scholar 

  2. Spuch C, Ortolano S, Navarro C (2012) New insights in the amyloid-beta interaction with mitochondria. J Aging Res 2012:324968. doi:10.1155/2012/324968

    Article  PubMed  PubMed Central  Google Scholar 

  3. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of Aβ accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15(9):1437–1449. doi:10.1093/hmg/ddl066

    Article  CAS  PubMed  Google Scholar 

  4. Du H, Yan SS (2010) Mitochondrial permeability transition pore in Alzheimer’s disease: cyclophilin D and amyloid beta. Biochim Biophys Acta 1802(1):198–204. doi:10.1016/j.bbadis.2009.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pinto M, Pickrell AM, Fukui H, Moraes CT (2013) Mitochondrial DNA damage in a mouse model of Alzheimer’s disease decreases amyloid beta plaque formation. Neurobiol Aging 34(10):2399–2407. doi:10.1016/j.neurobiolaging.2013.04.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309(5733):481–484. doi:10.1126/science.1112125

    Article  CAS  PubMed  Google Scholar 

  7. Sandhir R, Mehrotra A, Kamboj SS (2010) Lycopene prevents 3-nitropropionic acid-induced mitochondrial oxidative stress and dysfunctions in nervous system. Neurochem Int 57(5):579–587. doi:10.1016/j.neuint.2010.07.005

    Article  CAS  PubMed  Google Scholar 

  8. Kaur H, Chauhan S, Sandhir R (2011) Protective effect of lycopene on oxidative stress and cognitive decline in rotenone induced model of Parkinson’s disease. Neurochem Res 36(8):1435–1443. doi:10.1007/s11064-011-0469-3

    Article  CAS  PubMed  Google Scholar 

  9. Prema A, Janakiraman U, Manivasagam T, Thenmozhi AJ (2015) Neuroprotective effect of lycopene against MPTP induced experimental Parkinson’s disease in mice. Neurosci Lett 599:12–19. doi:10.1016/j.neulet.2015.05.024

    Article  CAS  PubMed  Google Scholar 

  10. Yi F, He X, Wang D (2013) Lycopene protects against MPP(+)-induced cytotoxicity by maintaining mitochondrial function in SH-SY5Y cells. Neurochem Res 38(8):1747–1757. doi:10.1007/s11064-013-1079-z

    Article  CAS  PubMed  Google Scholar 

  11. Fujita K, Yoshimoto N, Kato T, Imada H, Matsumoto G, Inakuma T, Nagata Y, Miyachi E (2013) Lycopene inhibits ischemia/reperfusion-induced neuronal apoptosis in gerbil hippocampal tissue. Neurochem Res 38(3):461–469. doi:10.1007/s11064-012-0952-5

    Article  CAS  PubMed  Google Scholar 

  12. Min JY, Min KB (2014) Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer’s disease mortality in older adults. Dement Geriatr Cognit Disord 37(3–4):246–256. doi:10.1159/000356486

    Article  CAS  Google Scholar 

  13. Sachdeva AK, Chopra K (2015) Lycopene abrogates Abeta(1–42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer’s disease. J Nutr Biochem 26(7):736–744. doi:10.1016/j.jnutbio.2015.01.012

    Article  CAS  PubMed  Google Scholar 

  14. Prakash A, Kumar A (2014) Implicating the role of lycopene in restoration of mitochondrial enzymes and BDNF levels in beta-amyloid induced Alzheimers disease. Eur J Pharmacol 741:104–111. doi:10.1016/j.ejphar.2014.07.036

    Article  CAS  PubMed  Google Scholar 

  15. Qu M, Zhou Z, Chen C, Li M, Pei L, Chu F, Yang J, Wang Y, Li L, Liu C, Zhang L, Zhang G, Yu Z, Wang D (2011) Lycopene protects against trimethyltin-induced neurotoxicity in primary cultured rat hippocampal neurons by inhibiting the mitochondrial apoptotic pathway. Neurochem Int 59(8):1095–1103. doi:10.1016/j.neuint.2011.10.005

    Article  CAS  PubMed  Google Scholar 

  16. Qu M, Nan X, Gao Z, Guo B, Liu B, Chen Z (2013) Protective effects of lycopene against methylmercury-induced neurotoxicity in cultured rat cerebellar granule neurons. Brain Res 1540:92–102. doi:10.1016/j.brainres.2013.10.005

    Article  CAS  PubMed  Google Scholar 

  17. Qu M, Li L, Chen C, Li M, Pei L, Chu F, Yang J, Yu Z, Wang D, Zhou Z (2011) Protective effects of lycopene against amyloid beta-induced neurotoxicity in cultured rat cortical neurons. Neurosci Lett 505(3):286–290. doi:10.1016/j.neulet.2011.10.048

    Article  CAS  PubMed  Google Scholar 

  18. Xu S, Zhong M, Zhang L, Wang Y, Zhou Z, Hao Y, Zhang W, Yang X, Wei A, Pei L, Yu Z (2009) Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells. FEBS J 276(14):3800–3809. doi:10.1111/j.1742-4658.2009.07094.x

    Article  CAS  PubMed  Google Scholar 

  19. Bhat AH, Dar KB, Anees S, Zargar MA, Masood A, Sofi MA, Ganie SA (2015) Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 74:101–110. doi:10.1016/j.biopha.2015.07.025

    Article  CAS  PubMed  Google Scholar 

  20. Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 304(5669):448–452. doi:10.1126/science.1091230

    Article  CAS  PubMed  Google Scholar 

  21. Hureau C, Faller P (2009) Abeta-mediated ROS production by Cu ions: structural insights, mechanisms and relevance to Alzheimer’s disease. Biochimie 91(10):1212–1217. doi:10.1016/j.biochi.2009.03.013

    Article  CAS  PubMed  Google Scholar 

  22. Parks JK, Smith TS, Trimmer PA, Bennett JP, Parker WD (2001) Neurotoxic Aβ peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J Neurochem 76(4):1050–1056. doi:10.1046/j.1471-4159.2001.00112.x

    Article  CAS  PubMed  Google Scholar 

  23. Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA (2002) Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem 80(1):91–100

    Article  CAS  PubMed  Google Scholar 

  24. Zhang Q, Yu J-T, Wang P, Chen W, Wu Z-C, Jiang H, Tan L (2011) Mitochondrial transcription factor A (TFAM) polymorphisms and risk of late-onset Alzheimer’s disease in Han Chinese. Brain Res 1368:355–360. doi:10.1016/j.brainres.2010.10.074

    Article  CAS  PubMed  Google Scholar 

  25. Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 7(12):548–554

    Article  CAS  PubMed  Google Scholar 

  26. Rizwan M, Rodriguez-Blanco I, Harbottle A, Birch-Machin MA, Watson RE, Rhodes LE (2011) Tomato paste rich in lycopene protects against cutaneous photodamage in humans in vivo: a randomized controlled trial. Br J Dermatol 164(1):154–162. doi:10.1111/j.1365-2133.2010.10057.x

    Article  CAS  PubMed  Google Scholar 

  27. Hong WK, Han EH, Kim DG, Ahn JY, Park JS, Han BG (2007) Amyloid-beta-peptide reduces the expression level of mitochondrial cytochrome oxidase subunits. Neurochem Res 32(9):1483–1488. doi:10.1007/s11064-007-9336-7

    Article  CAS  PubMed  Google Scholar 

  28. Yue R, Xia X, Jiang J, Yang D, Han Y, Chen X, Cai Y, Li L, Wang WE, Zeng C (2015) Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene. J Cell Physiol 230(9):2128–2141. doi:10.1002/jcp.24941

    Article  CAS  PubMed  Google Scholar 

  29. Choi H, Lee DG (2015) Lycopene induces apoptosis in Candida albicans through reactive oxygen species production and mitochondrial dysfunction. Biochimie 115:108–115. doi:10.1016/j.biochi.2015.05.009

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are particularly grateful to Dr. Fanzheng Yang (Central university of Finance and Economics) for her critical review and valuable suggestions that improved the quality of this manuscript.

Author information

Author notes

    Authors and Affiliations

    1. Center for Diseases Prevention and Control of the Rocket Force of PLA, Beijing, 100094, People’s Republic of China

      Mingyue Qu, Yuanxiang Liao & Xinzhong Nan

    2. Affiliated Hospital of Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China

      Zheng Jiang

    3. Center for Diseases Prevention and Control of the Air Force of PLA, Beijing, 100076, People’s Republic of China

      Zhenyao Song

    Authors
    1. Mingyue Qu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Zheng Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yuanxiang Liao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Zhenyao Song
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Xinzhong Nan
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Yuanxiang Liao.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    Mingyue Qu and Zheng Jiang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Qu, M., Jiang, Z., Liao, Y. et al. Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons. Neurochem Res 41, 1354–1364 (2016). https://doi.org/10.1007/s11064-016-1837-9

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s11064-016-1837-9

    Keywords

    Search

    Navigation