title: Inorganic arsenic induces apoptosis through downregulation of Ube2d genes and p53 accumulation in rat proximal tubular cells.
abstract: Ube2d ubiquitin-conjugating enzymes promote p53 ubiquitination and proteasomal degradation. We previously showed that cadmium induced p53-dependent apoptosis through the suppression of expression of Ube2d family genes (Ube2d1, Ube2d2, Ube2d3 and Ube2d4) in normal rat proximal tubular cells. Here we examined the effects of inorganic arsenic and inorganic mercury, which induce apoptosis in proximal tubular cells, on cellular protein level of p53 and gene expression of Ube2d family. Inorganic arsenic induced apoptosis with p53 accumulation, and suppressed Ube2d1, Ube2d2 and Ube2d4 expression, but not Ube2d3. On the other hand, although apoptosis was induced in response to inorganic mercury in proximal tubular cells, protein level of p53 was not elevated by inorganic mercury. These results suggest that inorganic arsenic, but not inorganic mercury, may induce p53-dependent apoptotic pathways through downregulation of gene expression of Ube2d family in proximal tubular cells.
authors.affiliation: Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University.
authors.forename: Maki
authors.initials: M
authors.lastname: Tokumoto
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Masanobu
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008627:Mercuric Chloride / Q000633:toxicity; D005810:Multigene Family; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D017670:Sodium Compounds / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics* / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018053:Arsenites; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; C017947:sodium arsenite; D008627:Mercuric Chloride; C097308:UBE2D1 protein, human; C097309:UBE2D2 protein, human; D044763:Ubiquitin-Conjugating Enzymes