Nitric oxide mediates intracytoplasmic and intranuclear zinc release

We previously described that NO · leads to destruction of ZnS clusters and release of Zn 2+ from various proteins including zinc finger transcription factors. To assess the relevance in living cells, we investigated, whether exogenous NO · leads to an increase of cytoplasmic and nuclear free Zn 2+. L929 cells, mouse splenocytes, or rat aorta endothelial cells were labeled with Zinquin-E, a Zn 2+-specific fluorophore, and were treated with two different spontaneous NO donors, S-nitroso-cysteine or DETA/NO. Both NO donors strongly increased the Zn 2+-dependent fluorescence in the cellular cytosol and also in nuclei as compared to controls. NO-dependent Zn 2+ release in splenocytes was quantitated by flow cytometry. These results show for the first time, that nitrosative stress mediates intracellular and intranuclear Zn 2+ release which may be relevant in altering gene expression patterns. © 1997 Federation of European Biochemical Societies.