Arsenite exposure in human lymphoblastoid cell lines induces autophagy and coordinated induction of lysosomal genes

Alicia M. Bolt, Randi M. Douglas, Walter Klimecki

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Chronic exposure to inorganic arsenic is associated with diverse, complex diseases, making the identification of the mechanism underlying arsenic-induced toxicity a challenge. An increasing body of literature from epidemiological and in vitro studies has demonstrated that arsenic is an immunotoxicant, but the mechanism driving arsenic-induced immunotoxicity is not well established. We have previously demonstrated that in human lymphoblastoid cell lines (LCLs), arsenic-induced cell death is strongly associated with the induction of autophagy. In this study we utilized genome-wide gene expression analysis and functional assays to characterize arsenic-induced effects in seven LCLs that were exposed to an environmentally relevant, minimally cytotoxic, concentration of arsenite (0.75 μM) over an eight-day time course. Arsenic exposure resulted in inhibition of cellular growth and induction of autophagy (measured by expansion of acidic vesicles) over the eight-day exposure duration. Gene expression analysis revealed that arsenic exposure increased global lysosomal gene expression, which was associated with increased functional activity of the lysosome protease, cathepsin D. The arsenic-induced expansion of the lysosomal compartment in LCL represents a novel target that may offer insight into the immunotoxic effects of arsenic.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalToxicology Letters
Volume199
Issue number2
DOIs
StatePublished - Nov 30 2010

Fingerprint

Autophagy
Arsenic
Genes
Cells
Cell Line
Gene expression
Gene Expression
arsenite
Cathepsin D
Cell death
Lysosomes
Toxicity
Assays
Peptide Hydrolases
Cell Death
Genome

Keywords

  • Arsenic
  • Autophagy
  • Lymphoblastoid
  • Lysosome
  • Microarray

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

Arsenite exposure in human lymphoblastoid cell lines induces autophagy and coordinated induction of lysosomal genes. / Bolt, Alicia M.; Douglas, Randi M.; Klimecki, Walter.

In: Toxicology Letters, Vol. 199, No. 2, 30.11.2010, p. 153-159.

Research output: Contribution to journalArticle

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