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Copper induces, and the copper chelator tetrathiomolybdate inhibits, activation of human aortic endothelial cells
Author(s) -
Wei Hao,
Zhang Weijian,
Frei Balz
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.695.2
Subject(s) - copper , chemistry , chemokine , ccl2 , chemotaxis , activator (genetics) , intracellular , cell adhesion molecule , monocyte , vcam 1 , inflammation , intercellular adhesion molecule 1 , cell adhesion , microbiology and biotechnology , cell , biochemistry , icam 1 , medicine , biology , receptor , organic chemistry
Copper may play an important role in enhancing oxidative stress and vascular inflammation. We investigated whether copper can induce activation of human aortic endothelial cells (HAECs), and whether copper chelation by tetrathiomolybdate (TTM) can inhibit this process. We found that incubating HAECs with 6.25 to 100 μM copper for 4 to 16 hrs dose‐ and time‐dependently up‐regulated vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1 (ICAM‐1), and monocyte chemotactic protein‐1 (MCP‐1) mRNA and cell surface protein levels. Maximum induction of VCAM‐1, ICAM‐1, and MCP‐1 mRNA levels (3.0±0.2, 4.2±0.8, and 5.8±1.4‐fold increase, respectively) was observed following incubation with 100 μM copper for 4 hrs. Maximum induction of cell surface protein levels of VCAM‐1 and ICAM‐1 was observed after 8 hrs of incubation with 100 μM copper (4.6±0.5 and 3.6±0.3‐fold increase, respectively). TTM in 10 μM significantly inhibited copper (100 μM) induced increases of surface protein levels of VCAM‐1 and ICAM‐1 by 67.0±4.9% and 78.2±4.8%, respectively. Furthermore, copper in 100 μM caused activation of activator protein 1 (AP‐1) and nuclear factor kappa B (NFκB) by 1.5±0.02 and 2.4±0.05 fold, respectively, which was significantly inhibited by TTM (10 μM). In conclusion, our data indicate that excessive copper may cause endothelial activation by up‐regulating expression of adhesion molecules and chemokines, and that TTM may be helpful in ameliorating copper‐induced vascular inflammation. This research was supported by NIH grant CERCAT, NIH P01 AT‐002034.