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

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-m...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2003-01, Vol.186 (2), p.101-109
Main Authors: Kirkpatrick, D.S, Dale, K.V, Catania, J.M, Gandolfi, A.J
Format: Article
Language:English
Subjects:
Animals
Arsenite
Arsenites - toxicity
As(III)
Biological and medical sciences
Cells, Cultured
Chemical and industrial products toxicology. Toxic occupational diseases
Cysteine Endopeptidases - drug effects
Cysteine Endopeptidases - metabolism
Dose-Response Relationship, Drug
HEK293 cells
Humans
Kidney Cortex - drug effects
Kidney Cortex - metabolism
Medical sciences
Metals and various inorganic compounds
Multienzyme Complexes - drug effects
Multienzyme Complexes - metabolism
Proteasome
Proteasome Endopeptidase Complex
Proteins - metabolism
Rabbit renal-cortical slices
Rabbits
Toxicology
Ubiquitin
Ubiquitin - metabolism
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Summary: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.
ISSN:0041-008X
1096-0333
DOI:10.1016/S0041-008X(02)00019-4