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 transcription factors. To assess the relevance in living cells, we investigated, whether exogenous NO. leads to an increase of cytoplasmic and nuclear free Zn2+. L929 cells, mouse splenocytes, or rat aorta endothelial cells were labeled with Zinquin-E, a Zn2+-specific fluorophore, and were treated with two different spontaneous NO donors, S-nitrosocysteine or DETA/NO. Both NO donors strongly increased the Zn2+-dependent fluorescence in the cellular cytosol and also in nuclei as compared to controls. NO-dependent Zn2+ release in splenocytes was quantitated by flow 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.
Berendji
D
D
Biomedical Research Centre, Heinrich-Heine University, Düsseldorf, Germany.
Kolb-Bachofen
V
V
Meyer
K L
KL
Grapenthin
O
O
Weber
H
H
Wahn
V
V
Kröncke
K D
KD
D000818:Animals; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005456:Fluorescent Dyes / Q000737:chemistry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry; D051381:Rats; D026403:S-Nitrosothiols; D013154:Spleen / Q000166:cytology; D014105:Tosyl Compounds / Q000737:chemistry; D014226:Triazenes / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism*
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D005456:Fluorescent Dyes; D015363:Quinolones; D026403:S-Nitrosothiols; D014105:Tosyl Compounds; D014226:Triazenes; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D015032:Zinc; D003545:Cysteine; C084731:zinquin