Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (17): 1858-1862.DOI: 10.6023/A12030026 Previous Articles     Next Articles

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连智慧a, 王海燕b, 王中奎a, 韩大雄a   

  1. a 厦门大学药学院 厦门 361005;
    b 国家海洋局第三海洋研究所 厦门 361005
  • 收稿日期:2012-05-06 出版日期:2012-09-14 发布日期:2012-07-06
  • 通讯作者: 韩大雄
  • 基金资助:
    项目受国家自然科学基金(No. 40976050)、海洋公益性项目(No. 201105013)和福建省重大专题项目(No. 2011YZ0001-1)资助

Effect of Free Amino Acids on the Abnormal Accumulation of Amyloid-β Peptides

Lian Zhihuia, Wang Haiyanb, Wang Zhongkuia, Han Daxionga   

  1. a School of Pharmaceutical Sciences, Xiamen University, Xiamen 361005;
    b Third Institute of Oceanography, State Oceanic Administration, Xiamen 361005
  • Received:2012-05-06 Online:2012-09-14 Published:2012-07-06
  • Supported by:
    Project supported by the National Natural Science Foundation of China (No. 40976050), the National Public Benefit (Ocean) Research Foundation of China (No. 201105013), and the Grand Research Foundation of Fujian Province (No. 2011YZ0001-1).

A major hallmark of Alzheimer’s disease is the senile plaques in cerebral cortex and hippocampus, mainly composed of the abnormal accumulation of amyloid-β (Aβ) peptides. It was suggested that metal ions (such as copper ions) would be a possible key mediating factor for the formation of amyloid deposits by binding to Aβ peptides and triggering the involved aggregation process. Some previous studies have uncovered that the concentration levels of free amino acids (aa) in the brain of AD patients are different from that of normal controls. So we investigated the interactions between copper ions and Aβ peptides in the presence of free amino acids. The effects of sixteen amino acids on the copper-Aβ complexes were examined by electrospray-ionization mass spectrometry (ESI-MS). Firstly, the mixture solution of Aβ(10-21) peptide (10 mmol/L) and Cu(Gly)2 (40 mmol/L) was incubated for 1 h at 37 ℃ in 10 mmol/L ammonium acetate buffer (pH=6.5). Then stock solution of each amino acid was added yielding Aβ/Cu2+/aa mixture solution at the final concentration of 1∶4∶x (x=0, 1, 2, 3, 4, 5, 10) for 200 mL total volume. After 1 h incubation, the samples were analyzed by ESI-MS. Different effects of these amino acids have been observed by comparing the mass spectrum of Aβ/Cu2+/aa mixture solution with the spectrum of Aβ/Cu2+mixture solution. Because of their side chain polarity and stronger coordination ability, Asp, Glu, Leu, Tyr, Thr and His can obviously inhibit the combination between copper ions and Aβ peptide at relative low concentrations, and Gln, Asn, Met, Ser and Cys can also inhibit the combination at moderate concentrations. However, Ala, Phe, Ile, Val and Lys can not inhibit at any concentration, and one of them, Lys, can even accelerate their combination. We infer that these amino acids which can inhibit the binding between Aβ peptides and copper ions may have relationships with the formation of the senile plaques and take into consideration that free amino acids may be a new kind of microenvironment factor related with the abnormal accumulation of Aβ peptides.

Key words: Alzheimer’s disease, amino acids, Aβ peptide, copper ions, ESI-MS