SODs are involved in the regulation of ICAM-1 expression in human melanoma and endothelial cells.
It is well known that ICAM-1 expression can be stimulated by TNF and by oxidative stress, via the activation of specific transcription factors. Two of these--NFkappaB and AP-1--can also be activated by reactive oxygen species, including the superoxide anion (also produced under TNF challenge). The latter is inactivated by superoxide dismutase of which two forms exist: Cu/Zn-SOD (cytoplasmic) and Mn-SOD (mitochondrial). We investigated whether superoxide anion direct generation or accumulation through specific SOD inhibition, may affect ICAM-1 expression in human melanoma and endothelial cells. Our results show a 20-50% increase in both SOD activities when cells were exposed to TNF or to an oxidative stress produced by Paraquat (a generator of superoxide anion radicals), both in terms of enzymes activity (zymogram) and protein levels (Western blotting and ELISA). Either with TNF or Paraquat, we could measure a significant increase of ICAM-1 expression with maxima ranging from 140 to 200%, depending on the cell line. Specific inhibition of Cu/Zn-SOD activity by DTIC (diethyldithiocarbamic acid), in presence of Paraquat or TNF, was followed by an upregulation of ICAM-1 expression (60 and 20%, respectively). In contrast, the addition of a SOD mimetic (MnTMPyP) completely inhibited Paraquat-stimulated ICAM-1 expression in melanoma cells and significantly decreased it in HUVEC (50%). In presence of TNF however, the same SOD mimetic inhibited TNF-stimulated ICAM-1 expression by 25% in melanoma and 17% in endothelial cells. In conclusion, these data provide evidence that melanoma and endothelial cells exposure to TNF or oxidative stress results in a significant increase of both Mn- and Cu/Zn-SOD activities. This increase seems to be associated with a reduction in the stimulation of ICAM-1 expression by TNF or oxidative stress.
Morandini
R
R
L.O.C.E., Institut J. Bordet, Université Libre de Bruxelles, Belgium. rmorand@resulb.ulb.ac.be
Boeynaems
J M
JM
Duhant
X
X
Jacquemotte
F
F
Kinnaert
E
E
Ghanem
G
G
D002478:Cells, Cultured / Q000187:drug effects; D003593:Cytoplasm / Q000201:enzymology; D003606:Dacarbazine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008665:Metalloporphyrins / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D007527:Isoenzymes; D008665:Metalloporphyrins; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D003606:Dacarbazine; D013482:Superoxide Dismutase; D010269:Paraquat