The Effect of Copper on Islet Amyloid Polypeptide Aggregation and Cytotoxicity — ASN Events
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  3. The Effect of Copper on Islet Amyloid Polypeptide Aggregation and Cytotoxicity

The Effect of Copper on Islet Amyloid Polypeptide Aggregation and Cytotoxicity (#45)

Mengrong Ma 1
  1. Department of Chemistry, Key Lab of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing, BJ, China

The pathogenesis of type 2 diabetes mellitus (T2DM) is associated with the aggregation of the 37-residue human islet amyloid polypeptide (hIAPP) into cytotoxic oligomers and fibrils[1]. It has been suggested that the cytotoxicity of hIAPP might be induced via an interaction with copper which may result in soluble oligomer formation[2], membrane destabilization[3], and oxidative stress[4]. However, it remains to be explored whether copper-mediated cytotoxicity is mainly due to reactive oxygen species (ROS) accumulation or other different mechanisms. Here our data support the view that copper-induced nanoscale oligomer formation played an important role in triggering cytotoxicity rather than ROS accumulation[5], suggesting it may be a valuable strategy to block the interaction of copper and hIAPP and therapeutics for T2DM.

  1. Hull, R. L.; Westermark, G. T.; Westermark, P.; Kahn, S. E. J. Clin. Endocrinol. Metab. 2004, 89, 3629.
  2. Ono, K.; Condron, M. M.; Teplow, D. B. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 14745.
  3. Quist, A.; Doudevski, I.; Lin, H.; Azimova, R.; Ng, D.; Frangione, B.; Kagan, B.; Ghiso, J.; Lal, R. Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 10427.
  4. Zraika, S.; Hull, R. L.; Udayasankar, J.; Aston-Mourney, K.; Subramanian, S. L.; Kisilevsky, R.; Szarek, W. A.; Kahn, S. E. Diabetologia 2009, 52, 626.
  5. Yu, Y. P.; Lei, P.; Hu, J.; Wu, W.H.; Zhao, Y. F.; Li, Y. M. Chem. Comm.2010, 46, 6909.