Copper, differently from zinc, affects the conformation, oligomerization state and activity of bradykinin.
The sole role of bradykinin (BK) as an inflammatory mediator is controversial, as recent data also support an anti-inflammatory role for BK in Alzheimer's disease (AD). The involvement of two different receptors (B1R and B2R) could be a key to understand this issue. However, although copper and zinc dyshomeostasis has been demonstrated to be largely involved in 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 the conformation and oligomerization of BK. In addition, we have correlated the chemical data with the effect of metals on the activity of BK analyzed in cell cultures by biochemical procedures. The biochemical analyses on monocyte/macrophage cell culture (THP-1 Cell Line human) in line with the effect of metals on the conformation of BK showed that the presence of copper can affect the signaling cascade mediated by the BK receptors. The results obtained show a further role of metal ions, particularly copper, in the development and outcome of neuroinflammatory diseases. The possible implications in AD are discussed.
Dipartimento di Scienze Biomediche e Biotecnologiche "BIOMETEC", Università degli Studi di Catania, Via S. Sofia 64, 95125 Catania, Italy. nicovigi@unict.it and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (C.I.R.C.M.S.B.), Piazza Umberto I, 1-70121 Bari, Italy.
Irina
I
Naletova
Dipartimento di Scienze Biomediche e Biotecnologiche "BIOMETEC", Università degli Studi di Catania, Via S. Sofia 64, 95125 Catania, Italy. nicovigi@unict.it and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (C.I.R.C.M.S.B.), Piazza Umberto I, 1-70121 Bari, Italy.
Vincenzo G
VG
Nicoletti
Istituto di Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Via Paolo Gaifami 18, 95126 Catania, Italy.
Danilo
D
Milardi
Dipartimento di Scienze della Salute, Università di Catanzaro, Campus Universitario, Viale Europa, 88100 Catanzaro, Italy.
Adriana
A
Pietropaolo
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, 95125, Catania, Italy. grassog@unict.it.
Giuseppe
G
Grasso
D001920:Bradykinin / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects*; D055503:Protein Multimerization / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*
D003300:Copper; D015032:Zinc; D001920:Bradykinin