Low-level arsenite causes accumulation of ubiquitinated proteins in rabbit renal cortical slices and HEK293 cells

D. S. Kirkpatrick, K. V. Dale, J. M. Catania, A. J. Gandolfi

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Arsenic is a known human carcinogen that affects a variety of processes within the cell. In this study, the effects of environmentally relevant As(III) exposures on the ubiquitin (Ub)-proteasome pathway have been investigated. Low-level As(III) exposure (0.5 - 10 μM) causes an accumulation of high-molecular-weight ubiquitin protein conjugates in both precision-cut rabbit renal-cortical slices and human embryonic kidney (HEK) 293 cells. The As(III) doses that induced these molecular changes were subcytotoxic in both model systems. Doses of 10 μM As(III) decreased cellular activity of the 20S proteasome by 40 and 15% in slices and HEK293 cells, respectively. As(III) did not cause any notable difference in Ub-conjugating activity of rabbit renal slices or HEK293 cells. Since ubiquitination plays such a vital role in maintaining cellular homeostasis, this noticeable perturbation of cellular ubiquitination is likely to have a multitude of signaling effects within the cells and may contribute to the pathogenesis of low-level arsenic.

Original languageEnglish (US)
Pages (from-to)101-109
Number of pages9
JournalToxicology and Applied Pharmacology
Volume186
Issue number2
DOIs
StatePublished - Jan 15 2003

Keywords

  • Arsenite
  • As(III)
  • HEK293 cells
  • Proteasome
  • Rabbit renal-cortical slices
  • Ubiquitin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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