Copper-homocysteine complexes and potential physiological actions

M D Apostolova, P R Bontchev, B B Ivanova, W R Russell, D R Mehandjiev, J H Beattie, C K Nachev

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

During the last 2 decades it was proposed that atherogenesis was closely related to the homeostasis of homocysteine (hCys) and/or copper. We hypothesized that the physiological action of hCys may be connected with its ability to form complexes with Cu. Our results showed the presence of two different Cu–hCys complexes. At a molar ratio Cu:hCys 1:1, a blue complex most probably consistent with a tentative dimeric CuII2(hCys)2(H2O)2 formula was formed, with tetrahedral Cu coordination and anti-ferromagnetic properties. The redox processes between Cu(II) and hCys, in a molar ratio =1:3 led to formation of a second yellow CuIhCys complex. Both Cu–hCys complexes affected the metabolism of extracellular thiols more than hCys alone and inhibited glutathione peroxidase-1 activity and mRNA abundance. The biological action of hCys and Cu–hCys complexes involved remodeling and phosphorylation of focal adhesion complexes and paxillin. The adhesive interactions of monocytes with an endothelial monolayer led to the redistribution of both paxillin and F-actin after all treatments, but the diapedesis of monocytes through endothelial cell monolayer was both greater and faster in the presence of the tentative CuII2(hCys)2(H2O)2 complex. Together, these observations suggest that Cu–hCys complexes actively participate in the biochemical responses of endothelial cells that are involved in the aethiopathogenesis of atherosclerosis.

Original languageEnglish
Pages (from-to)321-333
Number of pages13
JournalJournal of Inorganic Biochemistry
Volume95
Issue number4
Early online date27 May 2003
DOIs
Publication statusPublished - 1 Jul 2003

Keywords

  • homocysteine
  • copper
  • atherosclerosis
  • diapedesis
  • cell-line cultures
  • vascular-disease
  • crystal-structure
  • redox status
  • risk-factors
  • plasma
  • adhesion
  • cysteine
  • Hyperhomocysteinemia
  • artherosclerosis

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