抄録
We have found that the gene expression of Ube2d4, which is an ubiquitin-conjugating enzyme and one of Ube2d family, is depressed by cadmium (CdCl2; Cd) under non-toxic condition in rat proximal tubule cells (NRK-52E cells).
First of all, we investigated the effect of Cd on the gene expression of Ube2d family (Ube2d1/2/3/4) and the accumulation of p53 protein, which is ubiquitinated by Ube2d family, using NRK-52E cells. Cytotoxicity was detected by Cd (5 µM) treatment for 24 h, but not for 12 h. Ube2d family mRNA levels were markedly decreased and p53 protein levels were significantly increased before appearance of the cytotoxicity with Cd. On the other hand, Cd did not affect either p53 mRNA level or proteasome activity. At the end of Cd treatment for 24 h, apoptosis was induced through phosphorylation of p53.
Next, we examined the effect of arsenite (NaAsO2; As[III]) and inorganic mercury (HgCl2; Hg[II]), apoptosis inducing metals, on the expression of Ube2d family genes and cellular accumulation of p53 protein using NRK-52E cells. NRK-52E cells were treated with 20 µM As[III] and 50 µM Hg[II] for 6 or 24 h, and cytotoxicity of each metal was appearance at 24 h. As[III] as well as Cd induces p53-dependent apoptosis through suppression of the expression of Ube2d family, whereas Hg[II] induces p53-independent apoptosis.
These results suggest that overaccumulation of p53 through the suppression of gene expression of Ube2d family relate to Cd and As[III] cytotoxicity.
