Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells

Alicia M. Bolt, Fei Zhao, Samantha Pacheco, Walter Klimecki

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Epidemiological studies of arsenic-exposed populations have provided evidence that arsenic exposure in humans is associated with immunosuppression. Previously, we have reported that arsenite-induced toxicity is associated with the induction of autophagy in human lymphoblastoid cell lines (LCL). Autophagy is a cellular process that functions in the degradation of damaged cellular components, including protein aggregates formed by misfolded or damaged proteins. Accumulation of misfolded or damaged proteins in the endoplasmic reticulum (ER) lumen causes ER stress and activates the unfolded protein response (UPR). In an effort to investigate the mechanism of autophagy induction by arsenite in the LCL model, we examined the potential contribution of ER stress and activation of the UPR. LCL exposed to sodium arsenite for 8-days induced expression of UPR-activated genes, including CHOP and GRP78, at the RNA and the protein level. Evidence for activation of the three arms of the UPR was observed. The arsenite-induced activation of the UPR was associated with an accumulation of protein aggregates containing p62 and LC3, proteins with established roles in the sequestration and autophagic clearance of protein aggregates. Taken together, these data provide evidence that arsenite-induced autophagy is associated with the generation of ER stress, activation of the UPR, and formation of protein aggregates that may be targeted to the lysosome for degradation.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalToxicology and Applied Pharmacology
Volume264
Issue number2
DOIs
StatePublished - Oct 15 2012

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Unfolded Protein Response
Autophagy
Endoplasmic Reticulum Stress
Proteins
Arsenic
Cell Line
Chemical activation
Lysosomes
Endoplasmic Reticulum
Immunosuppression
arsenite
Epidemiologic Studies
Degradation
RNA
Protein Aggregates
Toxicity
Genes
Population
Cells

Keywords

  • Arsenite
  • Autophagy
  • ER stress
  • Lymphoblastoid cell lines
  • Proteotoxicity

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells. / Bolt, Alicia M.; Zhao, Fei; Pacheco, Samantha; Klimecki, Walter.

In: Toxicology and Applied Pharmacology, Vol. 264, No. 2, 15.10.2012, p. 255-261.

Research output: Contribution to journalArticle

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