Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese

Hitomi Fujishiro, Keisuke Kubota, Daisuke Inoue, Atsuhito Inoue, Takahiro Yanagiya, Shuichi Enomoto, Seiichiro Himeno

Research output: Contribution to journalArticle

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Abstract

The mechanism of cellular entry of cadmium remains unclear. We have previously established cadmium-resistant cells from mouse embryonic cells of metallothionein (MT)-null mice, and demonstrated that the down-regulation of a zinc transporter, Zrt/Irt-related protein (ZIP) 8, was responsible for the reduced cadmium incorporation into cells. In the present study, we developed cadmium-resistant cells (A+70 and B+70) from mouse embryonic cells of MT-expressing wild-type mice. The LC50 values of CdCl2 for A+70 and B+70 cells were about 200μM while that of the parental cells was 30μM. We found that the cadmium resistance of these cells was conferred not only by enhanced expression of MT, but also by a decrease in cadmium accumulation. Since the uptake rates of cadmium into A+70 and B+70 cells were lowered, we determined the expression levels of the metal transporters and channels potentially involved in the cellular uptake of cadmium. We found a down-regulation of multiple transport systems, including ZIP8, divalent metal transporter 1 (DMT1), and α1 subunits of L-type (CaV1.2) and T-type (CaV3.1) voltage-dependent calcium channels, in A+70 and B+70 cells. Furthermore, A+70 and B+70 cells exhibited cross-resistance to cytotoxicity of MnCl2, probably due to a marked decrease in manganese uptake in these cells. These results suggest that the suppressed expression of ZIP8 and DMT1, which are known to have affinities for both cadmium and manganese, may be responsible for the reduction in the uptake, and consequently the cytotoxicity, of cadmium and manganese in A+70 and B+70 cells.

Original languageEnglish
Pages (from-to)118-125
Number of pages8
JournalToxicology
Volume280
Issue number3
DOIs
Publication statusPublished - Feb 27 2011

Fingerprint

Manganese
Cadmium
Metallothionein
Cytotoxicity
Down-Regulation
Cadmium Chloride
T-Type Calcium Channels
Calcium Channels
Null Lymphocytes
Metals
Cells

Keywords

  • Cadmium
  • DMT1
  • Manganese
  • Resistance
  • Transport
  • ZIP8

ASJC Scopus subject areas

  • Toxicology

Cite this

Fujishiro, H., Kubota, K., Inoue, D., Inoue, A., Yanagiya, T., Enomoto, S., & Himeno, S. (2011). Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese. Toxicology, 280(3), 118-125. https://doi.org/10.1016/j.tox.2010.12.002

Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese. / Fujishiro, Hitomi; Kubota, Keisuke; Inoue, Daisuke; Inoue, Atsuhito; Yanagiya, Takahiro; Enomoto, Shuichi; Himeno, Seiichiro.

In: Toxicology, Vol. 280, No. 3, 27.02.2011, p. 118-125.

Research output: Contribution to journalArticle

Fujishiro, H, Kubota, K, Inoue, D, Inoue, A, Yanagiya, T, Enomoto, S & Himeno, S 2011, 'Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese', Toxicology, vol. 280, no. 3, pp. 118-125. https://doi.org/10.1016/j.tox.2010.12.002
Fujishiro, Hitomi ; Kubota, Keisuke ; Inoue, Daisuke ; Inoue, Atsuhito ; Yanagiya, Takahiro ; Enomoto, Shuichi ; Himeno, Seiichiro. / Cross-resistance of cadmium-resistant cells to manganese is associated with reduced accumulation of both cadmium and manganese. In: Toxicology. 2011 ; Vol. 280, No. 3. pp. 118-125.
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