Copper-homocysteine complexes and potential physiological actions.
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 Cu(II)(2)(hCys)(2)(H(2)O)(2) formula was formed, with tetrahedral Cu coordination and anti-ferromagnetic properties. The redox processes between Cu(II) and hCys, in a molar ratio > or =1:3 led to formation of a second yellow Cu(I)hCys 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 Cu(II)(2)(hCys)(2)(H(2)O)(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.
Apostolova
Margarita D
MD
Department of Cellular Integrity, Rowett Research Institute, Aberdeen AB219SB, UK. m.apostolova@utoronto.ca
Bontchev
Panayot R
PR
Ivanova
Bojidarka B
BB
Russell
Wendy R
WR
Mehandjiev
Dimiter R
DR
Beattie
John H
JH
Nachev
Choudomir K
CK
D002151:Calorimetry; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D015394:Molecular Structure; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D013055:Spectrophotometry, Infrared
D009942:Organometallic Compounds; D006710:Homocysteine; D019000:Phosphotyrosine; D003300:Copper; D005979:Glutathione Peroxidase