Copper and zinc effects on bradykinin conformation, oligomerization and activity

Besides the role of bradykinin (BK) as an inflammatory mediator, this peptide has been also proposed to have an important anti-inflammatory role in Alzheimer’s Disease (AD) (1, 2). Although copper and zinc dyshomeostasis have been demonstrated to be largely involved with the development of AD, a detailed study of the interaction of BK with these two metal ions has never been addressed. In this work, we have applied mass spectrometry, circular dichroism as well as computational methods in order to assess if copper and zinc have the ability to modulate BK conformation and oligomerization or have an effect on its stability and proneness to degradation by insulin-degrading enzyme, a metalloprotease considered to be involved in AD (3). Moreover the biochemical analyses of BK activity on monocyte cell culture (THP 1 Cell Line human) confirmed the metals effect, showing changes in the signaling cascade mediated by the BK receptor. The results obtained open to further role of metal ions, particularly copper, in the development and outcome of neuroinflammatory diseases.[1] Viel T.A. and Buck H.S. 2011 Kallikrein-Kinin system mediated inflammation in Alzheimer's disease in vivo. Cur. Alzheimer Res. 8, 59–66.[2] Walker K., Perkins M. and Dray A. 1995 Kinins and kinin receptors in the nervous system, Neuroch. Int., 26, 1–26.[3] Bellia F. and Grasso G. 2014 The role of copper(II) and zinc(II) in the degradation of human and murine IAPP by insulin-degrading enzyme. J. Mass Spectrom. 49, 274–279.