The molecular mechanism for human metallothionein-3 to protect against the neuronal cytotoxicity of Aβ1-2 with Cu ions

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• 作者：Ying Luo (3)
  Yuxia Xu (2)
  Qingui Bao (3)
  Zhichun Ding (4)
  Cuiqing Zhu (2)
  Zhong-Xian Huang (4)
  Xiangshi Tan (1)
  
• 关键词：Aβ1-2 ; Aβ1-2 aggregation ; Alzheimer disease ; Zinc ; reconstituted human metallothionein ; 3 ; Cellular toxicity ; ROS
• 刊名：Journal of Biological Inorganic Chemistry
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：18
• 期：1
• 页码：39-47
• 全文大小：870KB
• 参考文献：1. Khachaturian ZS (1985) Arch Neurol 42:1097-104 CrossRef
  2. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Proc Natl Acad Sci USA 82:4245-249 CrossRef
  3. Glenner GG, Wong CW (1984) Biochem Biophys Res Commun 120:885-90 CrossRef
  4. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Mullerhill B (1987) Nature 325:733-36 CrossRef
  5. Vigopelfrey C, Lee D, Keim P, Lieberburg I, Schenk DB (1993) J Neurochem 61:1965-968 CrossRef
  6. Hardy J (1997) Trends Neurosci 20:154-59 CrossRef
  7. Hardy J, Selkoe DJ (2002) Science 297:353-56 CrossRef
  8. Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, Carey PR (2003) Biochemistry 42:2768-773 CrossRef
  9. Bush AI (2003) Trends Neurosci 26:207-14 CrossRef
  10. Smith DG, Cappai R, Barnham KJ (2007) Biochim Biophys Acta Biomembr 1768:1976-990 CrossRef
  11. Li F, Calingasan NY, Yu FM, Mauck WM, Toidze M, Almeida CG, Takahashi RH, Carlson GA, Beal MF, Lin MT, Gouras GK (2004) J Neurochem 89:1308-312 CrossRef
  12. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) J Neurol Sci 158:47-2 CrossRef
  13. Smith MA, Harris PLR, Sayre LM, Perry G (1997) Proc Natl Acad Sci USA 94:9866-868 CrossRef
  14. Bush AI, Pettingell WH, Multhaup G, Paradis MD, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE (1994) Science 265:1464-467 CrossRef
  15. Atwood CS, Moir RD, Huang XD, Scarpa RC, Bacarra NME, Romano DM, Hartshorn MK, Tanzi RE, Bush AI (1998) J Biol Chem 273:12817-2826 CrossRef
  16. Esler WP, Stimson ER, Jennings JM, Ghilardi JR, Mantyh PW, Maggio JE (1996) J Neurochem 66:723-32 CrossRef
  17. Balakrishnan R, Parthasarathy R, Sulkowski E (1998) J Pept Res 51:91-5 CrossRef
  18. Faller P, Hureau C (2009) Dalton Trans 1080-094
  19. Hureau C, Faller P (2009) Biochimie 91:1212-217 CrossRef
  20. Halliwell B, Gutteridge JMC (1984) Biochem J 219:1-4
  21. Meloni G, Sonois V, Delaine T, Guilloreau L, Gillet A, Teissie J, Faller P, Vasak M (2008) Nat Chem Biol 4:366-72 CrossRef
  22. Pedersen JT, Hureau C, Hemmingsen L, Heegaard NHH, Ostergaard J, Vasak M, Faller P (2012) Biochemisty 51:1697-706 CrossRef
  23. Ding Z-C, Teng X-C, Cai B, Wang H, Zheng Q, Wang Y, Zhou G-M, Zhang M-J, Wu H-M, Sun H-Z, Huang Z-X (2006) Biochem Biophys Res Commun 349:674-82 CrossRef
  24. Ding Z-C, Zheng Q, Cai B, Yu W-H, Teng X-C, Wang Y, Zhou G-M, Wu H-M, Sun H-Z, Zhang M-J, Huang Z-X (2007) J Biol Inorg Chem 12:1173-179 CrossRef
  25. Bao Q, Lu Y, Li W, Sun X, Zhu C, Li P, Huang Z-X, Tan X (2011) J Biol Inorg Chem 16(5):809-16 CrossRef
  26. Palmiter RD, Findley SD, Whitmore TE, Durnam DM (1992) Proc Natl Acad Sci USA 89:6333-337 CrossRef
  27. Uchida Y, Tomonaga M (1989) Brain Res 481:190-93 CrossRef
  28. Uchida Y, Takio K, Titani K, Ihara Y, Tomonaga M (1991) Neuron 7:337-47 CrossRef
  29. Faller P, Vasak M (1997) Biochemistry 36:13341-3348 CrossRef
  30. Hasler DW, Faller P, Vasak M (1998) Biochemistry 37:14966-4973 CrossRef
  31. Irie Y, Keung WM (2001) Biochem Biophys Res Commun 282:416-20 CrossRef
  32. Irie Y, Keung WM (2003) Brain Res 960:228-34 CrossRef
  33. Schagger H, Vonjagow G (1987) Anal Biochem 166:368-79 CrossRef
  34. Reinke AA, She HY, Gestwicki JE (2009) Bioorg Med Chem Lett 19:4952-957 CrossRef
  35. Smith DP, Ciccotosto GD, Tew DJ, Fodero-Tavoletti MT (2007) Biochemistry 46:2881-891 CrossRef
  36. Hou L, Zagorski MGJ (2007) Am Chem Soc 128:9260-261 CrossRef
  37. Syme CD, Nadal RC, Rigby SE, Viles JHJ (2004) Biol Chem 279:18169-8177 CrossRef
  38. Guilloreau L (2006) J Biol Inorg Chem 11:1024-038 CrossRef
  39. Ding Z-C, Teng X-C, Zhen Q, Ni F-Y, Cai B, Wang Y, Zhou G-M, Sun H-Z, Tan X-S, Huang Z-X (2009) Biometals 22:817-26 CrossRef
  
• 作者单位：Ying Luo (3)
  Yuxia Xu (2)
  Qingui Bao (3)
  Zhichun Ding (4)
  Cuiqing Zhu (2)
  Zhong-Xian Huang (4)
  Xiangshi Tan (1)
  
  3. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China
  2. State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai, China
  4. Department of Chemistry, Fudan University, Shanghai, 200433, China
  1. Department of Chemistry, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China
  
• ISSN：1432-1327

文摘

Aggregation and cytotoxicity of Aβ with redox-active metals in neuronal cells have been implicated in the progression of Alzheimer disease. Human metallothionein (MT) 3 is highly expressed in the normal human brain and is downregulated in Alzheimer disease. Zn7MT3 can protect against the neuronal toxicity of Aβ by preventing copper-mediated Aβ aggregation, abolishing the production of reactive oxygen species (ROS) and the related cellular toxicity. In this study, we intended to decipher the roles of single-domain proteins (α/β) and the α–οdomain–domain interaction of Zn7MT3 to determine the molecular mechanism for protection against the neuronal cytotoxicity of Aβ1-2 with copper ions. With this in mind, the α and β single-domain proteins, heterozygous β(MT3)–οMT1), and a linker-truncated mutant ?1-4 were prepared and characterized. In the presence/absence of various Zn7MT3 proteins, the Aβ1-2–Cu2+-mediated aggregation, the production of ROS, and the cellular toxicity were investigated by transmission electron microscopy, ROS assay by means of a fluorescent probe, and SH-SY5Y cell viability, respectively. The β domain cannot abolish Aβ1-2–Cu2+-induced aggregation, and neither the β domain nor the α domain can quench the production of ROS because of the redox cycling of Aβ–Cu2+. Similarly to wild-type Zn7MT3, the heterozygous β(MT3)–οMT1) possesses the characteristic of alleviating Aβ1-2 aggregation and oxidative stress to neuronal cells. Therefore, the two domains through the linker Lys-Lys-Ser form a cooperative unit, and each of them is indispensable in conducting its bioactivity. The α domain plays an important role in modulating the stability of the metal–thiolate cluster, and the α–οdomain–domain interaction through the linker is critical for its protective role in the brain.