NITRIC-OXIDE MEDIATES INTRACYTOPLASMIC AND INTRANUCLEAR ZINC RELEASE

We previously described that NO. leads to destruction of ZnS clusters and release of Zn2+ from various proteins including zinc finger transc ription factors, To assess the relevance in living cells, we investiga ted, whether exogenous NO. leads to an increase of cytoplasmic and nuc lear free Zn2+. L929 cells, mouse splenocytes, or rat aorta endothelia l cells were labeled with Zinquin-E, a Zn2+-specific fluorophore, and were treated with two different spontaneous NO donors, S-nitrosocystei ne or DETA/NO. Both NO donors strongly increased the Zn2+-dependent fl uorescence in the cellular cytosol and also in nuclei as compared to c ontrols, NO-dependent Zn2+ release in splenocytes was quantitated by f low cytometry, These results show for the first time, that nitrosative stress mediates intracellular and intranuclear Zn2+ release which may be relevant in altering gene expression patterns. (C) 1997 Federation of European Biochemical Societies.