Reduction of Cadmium Accumulation and Cadmium-induced Cytotoxicity by Manganese

Yanagiya Takahiro, Imura Nobumasa, Enomoto Shuichi, Himeno Seiichiro

doi:10.51029/jtnrs.18.0_141

<p>Cadmium ( Cd) is an environmental pollutant that causes adverse effects in organisms, however, it remains unclear how Cd enters cells. Metallothionein (MT) plays an important role in Cd detoxification. In a previous study, we demonstrated that Cd traverses cells partly via a high-affinity transport system for manganese (Mn) using a Cd-resistant cell line (Cd-rB5) from immortalized MT-null mouse fibroblasts and that the suppression of this pathway is one of the determinants of the reduced susceptibility to Cd in Cd-rB5 cells. To clarify the role of the transport system for Mn in the cytotoxicity of Cd. we investigated the modulation of cytotoxicity and accumulation of Cd by Mn. using Cd-rB5 and their parental cells. Simultaneous addition of MnCl₂ to a medium alleviated the cytotoxicity of Cd in parental cells dose-dependently. In parallel. the accumulation of Cd in parental cells was reduced by the addition of MnCl₂ in a dose dependent manner. However, simultaneous exposure of Cd-rB5 cells to Mn did not modulate the cytotoxicity and accumulation of Cd. These results suggest that Mn may act as a competitor for Cd in entering cells, leading to the reduction of cytotoxicity of Cd. The cytotoxicity and accumulation of Cd in MT-null parental cells was attenuated also by ZnCl₂. but not by CoCl₂. NiCl₂. FeSO₄ or CuCl₂. suggesting that Zn may also have an affinity to the transport system for Mn and Cd. Thus, in addition to MT. the inhibition of cellular Cd uptake by Mn may be an important factor for detoxification for Cd.</p>

Reduction of Cadmium Accumulation and Cadmium-induced Cytotoxicity by Manganese

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