Enoxaparin reduces H2O2-induced activation of human endothelial cells by a mechanism involving cell adhesion molecules and nuclear transcription factors.
There are data that document the anti-inflammatory effect of enoxaparin (EP) and its possible antioxidant potential. This study was designed to search for the antioxidant mechanism(s) of EP directly on endothelial cells exposed to an oxidant stimulus. For this purpose cultured human endothelial cells were exposed to nontoxic concentrations of hydrogen peroxide in the presence or absence of EP, and the adhesion of monocytes, the expression of cell adhesion molecules and transcription factors possibly involved in the process were tested. Adhesion assays, ELISA and Western blot analysis revealed that EP reduced monocyte adhesion, ICAM-1 and P-selectin expression, decreased the nuclear levels of c-Jun and p65 proteins, and diminished the phosphorylation of c-Jun protein, MAPK p38 and JNK. Together, the data demonstrate the antioxidant effect of EP and the involvement of ICAM-1, P-selectin, MAPK p38, JNK and the transcription factors NF-kappaB and AP-1 in the mechanism of action of this drug.
Manduteanu
Ileana
I
Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania. imanduteanu@simionescu.instcellbiopath.ro
Dragomir
Elena
E
Voinea
Manuela
M
Capraru
Monica
M
Simionescu
Maya
M
D000925:Anticoagulants / Q000494:pharmacology; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017984:Enoxaparin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005544:Forecasting; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D000925:Anticoagulants; D015815:Cell Adhesion Molecules; D017984:Enoxaparin; D016328:NF-kappa B; D019007:P-Selectin; D016755:Proto-Oncogene Proteins c-jun; D050863:Synaptotagmin I; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases