JBIC Journal of Biological Inorganic Chemistry

, Volume 22, Issue 7, pp 1065–1074 | Cite as

Regulation of the aggregation behavior of human islet amyloid polypeptide fragment by titanocene complexes

Original Paper
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Abstract

The aggregation of human islet amyloid polypeptide (hIAPP) is associated with type II diabetes. The misfolding of hIAPP induces amyloid deposition and causes β-cell dysfunction. Metal complexes are potential metallodrugs that may reverse the aggregation of amyloid peptides. hIAPP19-37 is a crucial fragment of the full-length hIAPP1-37 and contains typical aromatic residues and a core hydrophobic region. In this work, we studied the effects of titanocene complexes titanocene dichloride (1), titanocene salicylic acid complex (2), and titanocene methionine complex (3) on the aggregation behavior of hIAPP19-37. We also explored the possible interactions of these complexes with hIAPP19-37. Results demonstrated that the titanocene complexes could effectively inhibit the aggregation of hIAPP19-37. The complexes bound with hIAPP19-37 in a spontaneous and exothermic process through hydrophobic interaction. Moreover, complex 3 could significantly decrease the cytotoxicity of hIAPP19-37 and improve cell survival. These data provide a basis for the use of titanocene complexes as potential agents against amyloidosis.

Graphical Abstract

Keywords

Titanocene complex hIAPP19-37 Aggregation Interaction 
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Notes

Acknowledgements

We are grateful for the support of the National Natural Science Foundation of China (No. 21473251 and 21271185).

Supplementary material

775_2017_1484_MOESM1_ESM.pdf (792 kb)
Supplementary material 1 (PDF 791 kb)

References

  1. 1.
    Caughey B, Lansbury PT (2003) Annu Rev Neurosci 26:267–298CrossRefPubMedGoogle Scholar
  2. 2.
    Selkoe DJ (2001) Physiol Rev 81:741–766PubMedGoogle Scholar
  3. 3.
    Hardy J, Selkoe DJ (2002) Science 297:353–356CrossRefPubMedGoogle Scholar
  4. 4.
    Conway K, Lee SJ, Rochet JC, Ding T, Harper J, Williamson R, Lansbury P (2000) Ann NY Acad Sci 920:42–45CrossRefPubMedGoogle Scholar
  5. 5.
    Forloni G, Angeretti N, Chieas R, Monzani E, Salmona M, Bugiani O, Tagliavini F (1993) Nature 362:543–546CrossRefPubMedGoogle Scholar
  6. 6.
    Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, Bates GP, Lehrach H, Wanker EE (1999) Proc Natl Acad Sci USA 96:4604–4609CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ray SS, Lansbury SS (2004) Proc Natl Acad Sci USA 101:5701–5702CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Westermark P, Wernstedt C, Wilander E, Sletten K (1986) Biochem Biophys Res Commun 140:827–831CrossRefPubMedGoogle Scholar
  9. 9.
    Epstein FH, Hoppener JW, Ahren B, Lips CJ (2000) N Engl J Med 343:411–419CrossRefGoogle Scholar
  10. 10.
    Cooper G, Willis A, Clark A, Turner R, Sim R, Reid K (1987) Proc Natl Acad Sci USA 84:8628CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nishi M, Chan SJ, Nagamatsu S, Bell GI, Steiner DF (1989) Proc Natl Acad Sci USA 86(15):5738–5742CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Clark A, Charge S, Badman M, Koning E (1996) Apmis 104(1–6):12–18CrossRefPubMedGoogle Scholar
  13. 13.
    Westermark P, Andersson A, Westermark GT (2011) Physiol Rev 91:795–826CrossRefPubMedGoogle Scholar
  14. 14.
    Li XL, Chen T, Wong XS, Xu G, Fan RR, Zhao HL, Chan JC (2011) Int J Biochem Cell Biol 43:525–534CrossRefPubMedGoogle Scholar
  15. 15.
    Hull RL, Weatermark GT, Kahn SE (2004) J Clin Endocrinol Metab 89(8):3629–3643CrossRefPubMedGoogle Scholar
  16. 16.
    Wiltzius JJ, Landau M, Nelson R, Saways MR, Apostol MI, Goldschmidt L, Soriaga AB, Cascio D, Rajashankar K, Eisenberg D (2009) Nat Struct Mol Biol 16(9):973–978CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Saraogi I, Hebda JA, Becerril J, Estroff LA, Miranker AD, Hamilton AD (2010) Angew Chem 122(4):748–751CrossRefGoogle Scholar
  18. 18.
    Brown DR, Schmidt B, Kretzschmar HA (1996) Nature 380:345–347CrossRefPubMedGoogle Scholar
  19. 19.
    Kapurniotu A (2001) Biopolymers 60:438–459CrossRefPubMedGoogle Scholar
  20. 20.
    de Groot SN, Pallarés I, Avilés FX, Vendrell J, Ventura S (2005) BMC Struct Biol 5:18CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Abedini A, Raleigh DP (2006) J Mol Biol 355:274–281CrossRefPubMedGoogle Scholar
  22. 22.
    Fox A, Snollaerts T, Casanova CE, Calciano A, Nogaj LA, Moffet DA (2010) Biochem 49:7783–7789CrossRefGoogle Scholar
  23. 23.
    Jaikaran ETAS, Higham CE, Serpell LC, Zurdo J, Gross M, Clark A, Fraser PE (2001) J Mol Biol 308:515–525CrossRefPubMedGoogle Scholar
  24. 24.
    Azriel R, Gazit E (2001) J Biol Chem 276:34156–34161CrossRefPubMedGoogle Scholar
  25. 25.
    Tenidis K, Waldner M, Bernhagen J, Fischle W, Bergmann M, Weber M, Merkle ML, Voelter W, Brunner H, Kapurniotu A (2000) J Mol Biol 295:1055–1071CrossRefPubMedGoogle Scholar
  26. 26.
    Scrocchi LA, Chen Y, Waschu KS, Wang F, Cheung S, Darabie AA, McLaurin J, Fraser PE (2002) J Mol Biol 318:697–706CrossRefPubMedGoogle Scholar
  27. 27.
    Zhang X, Cheng B, Gong H, Li C, Chen H, Zheng L, Huang K (2011) FEBS Lett 585:71–77CrossRefPubMedGoogle Scholar
  28. 28.
    Kapurniotu A (2001) Pept Sci 60(6):438–459CrossRefGoogle Scholar
  29. 29.
    Jung Y, Lippard SJ (2007) Chem Rev 107:1387–1407CrossRefPubMedGoogle Scholar
  30. 30.
    Yan K, Lok CN, Bierla K, Che CM (2010) Chem Commun 46:7691–7693CrossRefGoogle Scholar
  31. 31.
    Chen H, Parkinson JA, Parsons S, Robert RA, Gould RO, Sadler PJ (2002) J Am Chem Soc 124:3064–3082CrossRefPubMedGoogle Scholar
  32. 32.
    Fonteh P, Meyer D (2014) BMC Infect Dis 14:680CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Frik M, Jiménez J, Gracia I, Falvello LR, Abi-Habib S, Suriel K, Muth TR, Contel M (2012) Chemistry 18(12):3659–3674CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    He L, Wang X, Zhao C, Zhu D, Du W (2014) Metallomics 6:1087–1096CrossRefPubMedGoogle Scholar
  35. 35.
    Berners-Price SJ, Filipovska A (2011) Metallomics 3:863–873CrossRefPubMedGoogle Scholar
  36. 36.
    Nobili S, Mini E, Landini I, Gabbiani C, Casini A, Messori L (2010) Med Res Rev 3:550–580Google Scholar
  37. 37.
    Perez-Quintanilla D, Gomez-Ruiz S, Zizak Z, Sierra I, Prashar S, del Hierro I, Fajardo M, Juranic ZD, Kaluderovic GN (2009) Chem Eur J 15:5588–5597CrossRefPubMedGoogle Scholar
  38. 38.
    Yu Y, Lei P, Hu J, Wu W, Zhao Y, Li Y (2010) Chem Commun 46:6909–56911CrossRefGoogle Scholar
  39. 39.
    Rivillas-Acevedo L, Sanchez-Lopez C, Amero C, Quintanar L (2015) Inorg Chem 54:3788–3796CrossRefPubMedGoogle Scholar
  40. 40.
    Brender JR, Krishnamoorthy J, Messina GML, Deb A, Vivekanandan S, La Rosa C, Penner-Hahna JE, Ramamoorthy A (2013) Chem Commun 49:3339–3341CrossRefGoogle Scholar
  41. 41.
    Ward B, Walker K, Exley C (2008) J Inorg Biochem 102:371–375CrossRefPubMedGoogle Scholar
  42. 42.
    Brender JR, Hartman K, Nanga RPR, Popovych N, de la Salud Bea R, Vivekanandan S, Marsh ENG, Ramamoorthy A (2010) J Am Chem Soc 132:8973–8983CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Wang X, Cui M, Zhao C, He L, Zhu D, Wang B, Du W (2014) Inorg Chem 53:5044–5054CrossRefPubMedGoogle Scholar
  44. 44.
    Wang Y, Xu J, Wang L, Zhang B, Du W (2010) Chem Eur J 16:13339–13342CrossRefPubMedGoogle Scholar
  45. 45.
    Barnham KJ, Kenche VB, Ciccotosto GD, Smith DP, Tew DJ, Liu X, Perez K, Cranston GA, Johanssen TJ, Volitakis I, Bush AI, Masters CL, White AR, Smith JP, Cherny RA, Cappai R (2008) Proc Natl Acad Sci USA 105:6813–6818CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    He L, Wang X, Zhao C, Wang H, Du W (2013) Metallomics 5:1599–1603CrossRefPubMedGoogle Scholar
  47. 47.
    Wang X, Zhang B, Zhao C, Wang Y, He L, Cui M, Zhu X, Du W (2013) J Inorg Biochem 128:1–10CrossRefPubMedGoogle Scholar
  48. 48.
    Zhu D, Zhao C, Wang X, Wang W, Wang B, Du W (2016) RSC Adv 6:16055–16065CrossRefGoogle Scholar
  49. 49.
    Wang X, He L, Zhao C, Du W, Lin J (2013) J Biol InorgChem 18:767–778CrossRefGoogle Scholar
  50. 50.
    Chimento A, Saturnino C, Iacopetta D, Mazzotta R, Caruso A, Plutinoc MR, Mariconda A, Ramunno A, Sinicropi MS, Pezzi V, Longo P (2015) Bioorg Med Chem 23:7302–7312CrossRefPubMedGoogle Scholar
  51. 51.
    Gomez-Ruiz S, Kaluderovic GN, Prashar S, Polo-Ceron D, Fajardo M, Zizak Z, Sabo TJ, Juranic ZD (2008) J Inorg Biochem 102:1558–1570CrossRefPubMedGoogle Scholar
  52. 52.
    Chen X, Zhou L (2010) J Mol Struct Theochem 940:45–49CrossRefGoogle Scholar
  53. 53.
    Koubkova L, Vyzula R, Karban J, Pinkas J, Ondrouskova E, Vojtesek B, Hrstka R (2015) Invest New Drugs 33:1123–1132CrossRefPubMedGoogle Scholar
  54. 54.
    Laiva AL, Venugopal JR, Karuppuswamy P, Navaneethan BG, Ramakrishna S (2015) Int J Pharm 483(1–2):115–123CrossRefPubMedGoogle Scholar
  55. 55.
    Eger S, Immel TA, Claffey J, Muller-Bunz H, Tacke M, Grothand U, Huhn T (2010) Inorg Chem 49:1292–1294CrossRefPubMedGoogle Scholar
  56. 56.
    Guo M, Sun H, McArdle JH, Gambling L, Sadle JP (2000) Biochemistry 39:10023–10033CrossRefPubMedGoogle Scholar
  57. 57.
    Kröger N, Kleeberg UR, Mross K, Edler L, Hossfeld DK (2000) Onkologie 23:60–62Google Scholar
  58. 58.
    Lümmen G, Sperling H, Luboldt H, Otto T, Rübben H (1998) Cancer Chemother Pharmacol 42(5):415–417CrossRefPubMedGoogle Scholar
  59. 59.
    Marek P, Abedini A, Song BB, Kanungo M, Johnson ME, Gupta R, Zaman W, Wong SS, Raleigh DP (2007) Biochem 46:3255–3261CrossRefGoogle Scholar
  60. 60.
    Gao Z, Hu D, Gao L, Zhang X, Zhang Z, Liang Q (2001) J Organomet Chem 629:47–53CrossRefGoogle Scholar
  61. 61.
    Klapotke TM, Kopf H, Tornieporth-Oetting IC, White PS (1994) Organometallics 13:3628–3633CrossRefGoogle Scholar
  62. 62.
    He L, Zhu D, Zhao C, Xu J, Wang X, Du W (2015) J Inorg Biochem 152:114–122CrossRefPubMedGoogle Scholar
  63. 63.
    Khurana R, Coleman C, Ionescu-Zanetti C, Carter SA, Krishna V, Grover RK, Roy R, Singh SJ (2005) Struct Biol 151:229–238CrossRefGoogle Scholar
  64. 64.
    Gong G, Wang W, Du W (2017) RSC Adv 7:18512–18522CrossRefGoogle Scholar
  65. 65.
    Perez-Pineiro R, Bjorndahl TC, Berjanskii MV, Hau D, Li L, Huang A, Lee R, Gibbs E, Ladner C, Dong YW, Abera A, Cashman NR, Wishart DS (2011) FEBS J 278(2):4002–4014CrossRefPubMedGoogle Scholar
  66. 66.
    Phu MJ, Hawbecker SK, Narayanaswami V (2005) J Neurosci Res 80(6):877–886CrossRefPubMedGoogle Scholar
  67. 67.
    Okamura N, Mori M, Furumoto S, Yoshikawa T, Harada R, Ito S, Fujikawa Y, Arai H, Yanai K, Kudo YJ (2011) Alzheimer’s Dis 23(1):37–48Google Scholar
  68. 68.
    Qin K, Coomaraswamy J, Mastrangelo P, Yang Y, Lugowski S, Petromilli C, Prusiner SB, Fraser PE, Goldberg JM, Chakrabartty A, Westaway D (2003) J Biol Chem 278(11):8888–8896CrossRefPubMedGoogle Scholar
  69. 69.
    Jiang D, Li X, Williams R, Patel S, Men L, Wang Y, Zhou F (2009) Biochemistry 48:7939–7947CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    De Carufel CA, Nguyen PT, Sahnouni S, Bourgault S (2013) Biopolymers 100:645–655CrossRefPubMedGoogle Scholar
  71. 71.
    Zawisza I, Rózga M, Bal W (2012) Coord Chem Rev 256:2279–2307CrossRefGoogle Scholar
  72. 72.
    Yokoyama K, Fisher AD, Amori AR, Welchons DR, McKnight RE (2010) J Biophys Chem 1:153–163CrossRefGoogle Scholar
  73. 73.
    Anand U, Mukherjee M (2013) Langmuir 29:2713–2721CrossRefPubMedGoogle Scholar
  74. 74.
    Salamekh S, Brender JR, Hyung SJ, Nanga RP, Vivekanandan S, Ruotolo BT, Ramamoorthy A (2011) J Mol Biol 410(2):294–306CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Ross PD, Subramanian S (1981) Biochem 20(11):3096–3102CrossRefGoogle Scholar
  76. 76.
    Hu YJ, Ou-Yang Y, Dai CM, Liu Y, Xiao XH (2010) Biomacromol 11:106–112CrossRefGoogle Scholar
  77. 77.
    Zhu D, Gong G, Wang W, Du W (2017) J Inorg Biochem 170:109–116CrossRefPubMedGoogle Scholar
  78. 78.
    Cheng B, Liu X, Gong H, Huang L, Chen H, Zhang X, Li C, Yang M, Ma B, Jiao L, Zheng L, Huang K (2011) J Agric Food Chem 59:13147–13155CrossRefPubMedGoogle Scholar
  79. 79.
    Grabenauer M, Wu C, Soto P, Shea JE, Bowers MT (2010) J Am Chem Soc 132:532–539CrossRefPubMedGoogle Scholar
  80. 80.
    Walsh P, Neudecker P, Sharpe S (2010) J Am Chem Soc 132(22):7684–7695CrossRefPubMedGoogle Scholar
  81. 81.
    Bartolini M, Bertucci C, Bolognesi ML, Cavalli A, Melchiorre C, Andrisano V (2007) ChemBioChem 8(17):2152–2161CrossRefPubMedGoogle Scholar
  82. 82.
    Mompean M, Gonzalez C, Lomba E, Laurents DV (2014) J Phys Chem B 118(26):7312–7316CrossRefPubMedGoogle Scholar
  83. 83.
    Vigneswara V, Cass S, Wayne D, Bolt EL, Ray DE, Carter WG (2013) PLoS One 8(4):e61442CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Lee SJC, Choi TS, Lee WH, Lee HJ, Mun DG, Akashi S, Lee SW, Lim MH, Kim HI (2016) Chem Sci 7:5398–5406CrossRefGoogle Scholar
  85. 85.
    Wang W, Zhao C, Zhu D, Gong G, DU W (2017) J Inorg Biochem 171:1–9CrossRefPubMedGoogle Scholar

Copyright information

© SBIC 2017

Authors and Affiliations

  1. 1.Department of ChemistryRenmin University of ChinaBeijingChina

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