Sodium arsenite enhances AP-1 and NFκB DNA binding and induces stress protein expression in precision-cut rat lung slices

Jayanthika B. Wijeweera, A. Jay Gandolfi, Alan Parrish, R. Clark Lantz

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Arsenic is a known human carcinogen. These studies were designed to examine the impact of low arsenite concentrations on immediate early gene expression in precision-cut rat lung slices. Precision-cut lung slices are a versatile in-vitro system for toxicity studies, as they preserve the architecture and cellular heterogeneity of the lung. Since 0.1-100 μM arsenite did not compromise slice viability at 4 hours, effects of arsenite on the expression of c-jun/AP-1, NFκB, HSP 32, HSP 72, HSP 60, and HSP 90 were studied, using these concentrations of arsenete at 4 h. Nuclear c-jun was increased by 10 and 100 μM arsenite, while NFκB was not affected. Gel-shift assays indicated that 10 μM arsenite resulted in an enhanced DNA-binding activity of both AP-1 and NFκB. Confocal microscopic analysis of AP-1 indicated nuclear localization of this transcription factor, mainly in type-II epithelial cells and alveolar macrophages. Nuclear localization of NFκB was lower than that observed for AP-1, while most of the NFκB was localized to cytoplasm of type-II epithelial cells and alveolar macrophages. HSP 32 was increased by 1.0 and 10 μM arsenite, while HSP 72 was increased by only 100 μM arsenite. HSP 60 and HSP 90 were not changed by arsenite. These studies indicate that noncytotoxic concentrations of arsenite are capable of affecting signal transduction pathways and gene expression in the lung.

Original languageEnglish (US)
Pages (from-to)283-294
Number of pages12
JournalToxicological Sciences
Volume61
Issue number2
DOIs
StatePublished - 2001

Keywords

  • AP-1
  • In vitro
  • NFκB
  • Precision-cut lung slices
  • Sodium arsenite
  • Stress proteins

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Sodium arsenite enhances AP-1 and NFκB DNA binding and induces stress protein expression in precision-cut rat lung slices'. Together they form a unique fingerprint.

Cite this