NOR-3, a donor of nitric oxide, increases intracellular Zn2+ concentration and decreases cellular thiol content: A model experiment using rat thymocytes, FluoZin-3, and 5-chloromethylfluorescein

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Our previous study showed that nitroprusside, a donor of nitric oxide (NO), increased intracellular Zn2+concentration without affecting cellular content of glutathione (GSH) although it has been proposed that thecytotoxicity of NO is resulted from its interaction with glutathione and zinc. Nitroprusside releases not onlyNO but also cyanides (Fe(II)CN and Fe(III)CN), CN-, Fe2+, and Fe3+. Therefore, such decomposition productsmay mask NO-induced action on cellular GSH content. In this study, we used NOR-3 as a donor of NO toreveal the effects of NO on intracellular Zn2+ concentration and cellular GSH content in a cytometric mannerwith fluorescent probes, FluoZin-3-AM and 5-chloromethylfluorescein diacetate. NOR-3 at 1-3 mMsignificantly increased intracellular Zn2+ concentration and decreased cellular GSH content. After the removalof extracellular Zn2+ by diethylenetriamine-N,N,N',N",N"-pentaacetic acid (DTPA, a chelator for Zn2+), theincrease in intracellular Zn2+ concentration by NOR-3 was still observed although DTPA significantly attenuatedthe increase in intracellular Zn2+ concentration by NOR-3. Results suggest an involvement of both intracellularZn2+ release and increase in membrane Zn2+ permeability. It is likely that NO induces oxidative stress, leadingto an increase in intracellular Zn2+ concentration.