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J.Health Sci., 54(3), 339-342, 2008

Enhancement of Nuclear Localization of Metallothionein by Nitric Oxide

Yasumitsu Ogra,* Saki Onishi, Asami Kajiwara, Atsuko Hara, and Kazuo T. Suzuki

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan

Nitric oxide (NO) enhanced the nuclear localization of metallothionein (MT) in digitoninpermeabilized semi-intact HeLa cells. Although 1-Hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC5), an NO donor, enhanced the nuclear localization of MT in a manner similar to hydrogen peroxide (H2O2), a tenfold higher concentration of NOC5 was required to achieve the same effect as H2O2, suggesting that an endogenous NO scavenger existed in the reaction mixture of the nuclear import assay system that we used. We also evaluated the effect of NO on the nuclear localization of MT in intact HeLa cells. Treatment with NOC5 induced the nuclear localization of MT pre-induced with zinc, and its effect was greater than that of H2O2. The induced MT was localized in the nucleus and the cytoplasm. The results suggest that MT can scavenge NO using the sulfhydryl groups of cysteines in its molecule to form nitrosothiol, thereby reducing nuclear and cytoplasmic damage by NO.