Nanomedicine: Nanotechnology, Biology and Medicine
Volume 7, Issue 1 , Pages 107-114 , February 2011

C60 fullerene-pentoxifylline dyad nanoparticles enhance autophagy to avoid cytotoxic effects caused by the β-amyloid peptide

  • Chi-Ming Lee, MS

      Affiliations

    • Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
    • Instrument Center, Taipei Medical University, Taipei, Taiwan
    • These two authors contributed equally to this work.
  • ,
  • Sheng-Tung Huang, PhD

      Affiliations

    • Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan
    • These two authors contributed equally to this work.
  • ,
  • Shih-Hao Huang, PhD

      Affiliations

    • Department of Food Science, Taipei College of Maritime Technology, Taipei, Taiwan
  • ,
  • Hui-Wen Lin, PhD

      Affiliations

    • Biostatistic Research and Consulting Center, Taipei Medical University, Taipei, Taiwan
  • ,
  • Hsiang-Ping Tsai, MS

      Affiliations

    • Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
    • School of Medicine, Taipei Medical University, Taipei, Taiwan
  • ,
  • Jui-Yu Wu, PhD

      Affiliations

    • School of Medicine, Taipei Medical University, Taipei, Taiwan
  • ,
  • Chun-Mao Lin, PhD

      Affiliations

    • School of Medicine, Taipei Medical University, Taipei, Taiwan
    • Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan
    • Corresponding Author InformationCorresponding author: School of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • ,
  • Chien-Tsu Chen, PhD

      Affiliations

    • School of Medicine, Taipei Medical University, Taipei, Taiwan

Received 2 February 2010 ,Accepted 26 June 2010.

References 

  1. Zheng L, Marcusson J, Terman A. Oxidative stress and Alzheimer disease: the autophagy connection?. Autophagy. 2006;2:143–145
  2. Zhang H, Kong X, Kang J, Su J, Li Y, Zhong J, et al. Oxidative stress induces parallel autophagy and mitochondria dysfunction in human glioma U251 cells. Toxicol Sci. 2009;110:376–388
  3. Harhaji-Trajkovic L, Vilimanovich U, Kravic-Stevovic T, Bumbasirevic V, Trajkovic V. AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumor cells. J Cell Mol Med. 2009;13:3644–3654
  4. Black RS, Barclay LL, Nolan KA, Thaler HT, Hardiman ST, Blass JP. Pentoxifylline in cerebrovascular dementia. J Am Geriatr Soc. 1992;40:237–244
  5. Solerte SB, Ceresini G, Ferrari E, Fioravanti M. Hemorheological changes and overproduction of cytokines from immune cells in mild to moderate dementia of the Alzheimer's type: adverse effects on cerebromicrovascular system. Neurobiol Aging. 2000;21:271–281
  6. Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004;226:67–70
  7. Hemmer CJ, Hort G, Chiwakata CB, Seitz R, Egbring R, Gaus W, et al. Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study. Am J Trop Med Hyg. 1997;56:397–403
  8. Sitharaman B, Zakharian TY, Saraf A, Misra P, Ashcroft J, Pan S, et al. Water-soluble fullerene (C60) derivatives as nonviral gene-delivery vectors. Mol Pharm. 2008;5:567–578
  9. Dugan LL, Turetsky DM, Du C, Lobner D, Wheeler M, Almli CR, et al. Carboxyfullerenes as neuroprotective agents. Proc Natl Acad Sci U S A. 1997;94:9434–9439
  10. Podolski IY, Podlubnaya ZA, Kosenko EA, Mugantseva EA, Makarova EG, Marsagishvili LG, et al. Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in vitro and performance of the cognitive task. J Nanosci Nanotechnol. 2007;7:1479–1485
  11. Gharbi N, Pressac M, Hadchouel M, Szwarc H, Wilson SR, Moussa F. [60]fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett. 2005;5:2578–2585
  12. Behl C, Moosmann B. Antioxidant neuroprotection in Alzheimer's disease as preventive and therapeutic approach. Free Radic Biol Med. 2002;33:182–191
  13. Wong-Ekkabut J, Baoukina S, Triampo W, Tang IM, Tieleman DP, Monticelli L. Computer simulation study of fullerene translocation through lipid membranes. Nat Nanotechnol. 2008;3:363–368
  14. Yamago S, Tokuyama H, Nakamura E, Kikuchi K, Kananishi S, Sueki K, et al. In vivo biological behavior of a water-miscible fullerene: 14C labeling, absorption, distribution, excretion and acute toxicity. Chem Biol. 1995;2:385–389
  15. Huang ST, Liao JS, Fang HW, Lin CM. Synthesis and anti-inflammation evaluation of new C60 fulleropyrrolidines bearing biologically active xanthine. Bioorg Med Chem Lett. 2008;18:99–103
  16. Huang ST, Ho CS, Lin CM, Fang HW, Peng YX. Development and biological evaluation of C(60) fulleropyrrolidine-thalidomide dyad as a new anti-inflammation agent. Bioorg Med Chem. 2008;16:8619–8626
  17. Lin HC, Tsai SH, Chen CS, Chang YC, Lee CM, Lai ZY, et al. Structure-activity relationship of coumarin derivatives on xanthine oxidase-inhibiting and free radical-scavenging activities. Biochem Pharmacol. 2008;75:1416–1425
  18. Harman AN, Kraus M, Bye CR, Byth K, Turville SG, Tang O, et al. HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. Blood. 2009;114:85–94
  19. Chang YC, Lee FW, Chen CS, Huang ST, Tsai SH, Huang SH, et al. Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase-inhibiting and free radical-scavenging activities. Free Radic Biol Med. 2007;43:1541–1551
  20. Keller JN, Guo Q, Holtsberg FW, Bruce-Keller AJ, Mattson MP. Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production. J Neurosci. 1998;18:4439–4450
  21. Verhoeven AJ, Verhaar R, Gouwerok EG, de Korte D. The mitochondrial membrane potential in human platelets: a sensitive parameter for platelet quality. Transfusion. 2005;45:82–89
  22. Huang SH, Lin CM, Chiang BH. Protective effects of Angelica sinensis extract on amyloid β-peptide-induced neurotoxicity. Phytomedicine. 2008;15:710–721
  23. Nakka VP, Gusain A, Raghubir R. Endoplasmic reticulum stress plays critical role in brain damage after cerebral ischemia/reperfusion in rats. Neurotox Res. 2009;17:189–202
  24. Soccio RE, Adams RM, Maxwell KN, Breslow JL. Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J Biol Chem. 2005;280:19410–19418
  25. Szaraz P, Banhegyi G, Benedetti A. Altered redox state of luminal pyridine nucleotides facilitates the sensitivity towards oxidative injury and leads to endoplasmic reticulum stress dependent autophagy in HepG2 cells. Int J Biochem Cell Biol. 2010;42:157–166
  26. Hoyer-Hansen M, Bastholm L, Szyniarowski P, Campanella M, Szabadkai G, Farkas T, et al. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2. Mol Cell. 2007;25:193–205
  27. Kroemer G, Levine B. Autophagic cell death: the story of a misnomer. Nat Rev Mol Cell Biol. 2008;9:1004–1010
  28. Huang Q, Wu YT, Tan HL, Ong CN, Shen HM. A novel function of poly(ADP-ribose) polymerase-1 in modulation of autophagy and necrosis under oxidative stress. Cell Death Differ. 2009;16:264–277
  29. Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid β accumulation in mice. J Clin Invest. 2008;118:2190–2199
  30. Sasnauskiene A, Kadziauskas J, Vezelyte N, Jonusiene V, Kirveliene V. Damage targeted to the mitochondrial interior induces autophagy, cell cycle arrest and, only at high doses, apoptosis. Autophagy. 2009;5:743–744
  31. Cheng Y, Qiu F, Ye YC, Guo ZM, Tashiro S, Onodera S, et al. Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-κB survival pathways in oridonin-treated murine fibrosarcoma L929 cells. FEBS J. 2009;276:1291–1306
  32. Marlatt MW, Lucassen PJ, Perry G, Smith MA, Zhu X. Alzheimer's disease: cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies. J Alzheimers Dis. 2008;15:199–210
  33. Gilmore JL, Yi X, Quan L, Kabanov AV. Novel nanomaterials for clinical neuroscience. J Neuroimmune Pharmacol. 2008;3:83–94
  34. Sha MC, Callahan CM. The efficacy of pentoxifylline in the treatment of vascular dementia: a systematic review. Alzheimer Dis Assoc Disord. 2003;17:46–54
  35. Beshay E, Croze F, Prud'homme GJ. The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo. Clin Immunol. 2001;98:272–279
  36. Andres-Barquin PJ, Hernandez MC, Israel MA. Id4 expression induces apoptosis in astrocytic cultures and is down-regulated by activation of the cAMP-dependent signal transduction pathway. Exp Cell Res. 1999;247:347–355
  37. Sliwa K, Woodiwiss A, Kone VN, Candy G, Badenhorst D, Norton G, et al. Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation. 2004;109:750–755
  38. Boucher M, Wann BP, Kaloustian S, Cardinal R, Godbout R, Rousseau G. Reduction of apoptosis in the amygdala by an A2A adenosine receptor agonist following myocardial infarction. Apoptosis. 2006;11:1067–1074
  39. Memmott RM, Dennis PA. Akt-dependent and -independent mechanisms of mTOR regulation in cancer. Cell Signal. 2009;21:656–664
  40. Lao F, Chen L, Li W, Ge C, Qu Y, Sun Q, et al. Fullerene nanoparticles selectively enter oxidation-damaged cerebral microvessel endothelial cells and inhibit JNK-related apoptosis. ACS Nano. 2009;3:3358–3368

 This study was supported by a grant (DOH99-TD-B-111-003) from the Center of Excellence for Clinical Trial and Research in Neuroscience.

 This study did not involve human or animal research.

PII: S1549-9634(10)00170-X

doi: 10.1016/j.nano.2010.06.009

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 7, Issue 1 , Pages 107-114 , February 2011