Chromium(III) complexes inhibit transcription factors binding to DNA and associated gene expression

Toxicology. 2008 Sep 29;251(1-3):61-5. doi: 10.1016/j.tox.2008.07.052. Epub 2008 Jul 26.

Abstract

Role of chromium(III) in biological systems is controversial and no significant conclusions can be arrived with the available data. Chromium(VI) enters in to the cell readily and gets reduced to form stable chromium(III) complexes. Chromium(III) complexes react slowly and were considered non-toxic. Recent studies suggest that chromium(III) indeed produce damage to cellular organelle, DNA and proteins and can be lethal to organisms and their offspring. Several chromium(III) complexes synthesized are shown to interact with DNA and bring changes in the conformation of DNA and proteins. In this work, effects of these interactions in the vital process like transcription have been studied. Three Cr(III) complexes with varied ligand environment, ionic character and charge have been chosen for the study to evaluate their ability to interrupt the binding of two different transcription factors Sp1 and TFIID, with their consensus sequences and interruption of the transcription process. Of the three complexes tested [Cr(salen)(H(2)O)(2)](+) is the most efficient inhibitor of transcription factors-DNA (TF-DNA) complex formation and transcription. Inhibition of TF-DNA complex formation and transcription by this complex is concentration-dependent. [Cr(pic)(3)] does not inhibit both TF-DNA complex formation and transcription. [Cr(ttpy)(2)](+3) inhibits TF-DNA complex formation at higher concentrations but does not inhibit transcription even at very high concentrations compared to that of [Cr(salen)(H(2)O)(2)](+). Results of these studies suggest that chromium(III) complexes, though less reactive can still interfere in the important biological process and this interactions are determined by the ligand environment around the complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell-Free System
  • Chromium / chemistry
  • Chromium / toxicity*
  • DNA* / chemistry
  • DNA* / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • Electrophoretic Mobility Shift Assay
  • Gene Expression / drug effects*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / toxicity*
  • Protein Binding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Transcription Factors* / chemistry
  • Transcription Factors* / genetics

Substances

  • DNA-Binding Proteins
  • Organometallic Compounds
  • Recombinant Proteins
  • Transcription Factors
  • Chromium
  • DNA