Cadmium toxicity is caused by accumulation of p53 through the down-regulation of Ube2d family genes in vitro and in vivo

• DOI: 10.2131/jts.36.191
• Publication Date: 2011-04-01T06:47:55Z
• Authors: Maki Tokumoto; Yasuyuki Fujiwara; Akinori Shimada; Tatsuya Hasegawa; Yoshiyuki Seko; Hisamitsu Nagase; Masahiko Satoh
• Keywords: 0303 health sciences; Cell Survival; Down-Regulation; Apoptosis; Epithelial Cells; Rats; 3. Good health; Kidney Tubules, Proximal; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cadmium Chloride; Ubiquitin-Conjugating Enzymes; Animals; Female; RNA, Messenger; Tumor Suppressor Protein p53; Cells, Cultured; Oligonucleotide Array Sequence Analysis

Cadmium (Cd) causes renal dysfunction with damage to kidney proximal tubule cells; however, the precise mechanisms of toxicity remain unclear. Previously, we found that expression Ube2d4 gene, which is a member ubiquitin-conjugating enzyme Ube2d family, suppressed by Cd in NRK-52E rat tubular epithelial cells. To investigate Cd-induced toxicity, examined effects on ubiquitin-proteasome system, particularly and function family members cells mice. markedly decreased Ube2d1, Ube2d2, Ube2d3 prior appearance cytotoxicity also dramatically increased p53 protein levels cells, without stimulation gene or inhibition proteasome activity. In addition, induced phosphorylation caused apoptosis vivo, effect orally administrated for 12 months genes accumulation mouse kidney. Chronic exposure suppression p53. did not induce severe injury, but tubules. These results suggest may be due degradation through down-regulation genes, induces p53-dependent Moreover, one critical targets Cd.