Modulation of the nitric oxide pathway by copper in glial cells.
The action of copper on the nitric oxide (NO) pathway was investigated in rat C6 glioma cells expressing both inducible and constitutive NO synthase (NOS) isoforms. The inducible NOS-II-mediated NO synthesis (i.e., nitrite production induced by LPS plus IFNgamma) was found to be increased upon copper uptake by cells, this effect being attributable to NOS-II mRNA transcriptional over-expression. On the other hand, the constitutive neuronal isoform (NOS-I) was inhibited after copper uptake, as revealed by the decrease of basal intracellular cGMP levels in C6 cells. Consistently, in vitro experiments showed that copper selectively blocked the catalytic activity of NOS-I, but not of NOS-II. The observed modulation of NOS isoforms by copper in C6 cells is in line with the previous hypothesis that selective inhibition of NOS-I leads to enhanced NO production through transcriptional activation of NOS-II.
Colasanti
M
M
Department of Biology, University 'ROMA TRE,', Viale G. Marconi 446, Rome, I-00146, Italy.
Persichini
T
T
Venturini
G
G
Polticelli
F
F
Musci
G
G
D000818:Animals; D001120:Arginine / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008070:Lipopolysaccharides; D009573:Nitrites; D012333:RNA, Messenger; D002956:Citrulline; D009569:Nitric Oxide; D003300:Copper; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D006152:Cyclic GMP