Chromium(III) triggers the DNA-damaged checkpoint of the cell cycle and induces a functional increase of 4E-BP

Chem Res Toxicol. 2008 Feb;21(2):542-9. doi: 10.1021/tx700244h. Epub 2008 Jan 16.

Abstract

Using sea urchin early embryos as a pertinent model, chromium(III) provoked cell cycle arrest and induced apoptosis. The molecular machinery of translation initiation was investigated. Chromium provoked a time- and dose-dependent increase in the level of 4E-BP protein, the natural regulator of the cap-dependent initiation factor 4E (eIF4E). The 4E-BP increase was the result of 4E-BP stabilization and appeared functional for physiological eIF4E binding, removal of eIF4E from the initiation factor eIF4G, and almost full inhibition of cap-dependent translation in vivo. The protein 4E-BP may be involved in the biological pathway of apoptosis associated with the activation of the DNA-damaged checkpoint of the cell cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Chlorides / toxicity*
  • Chromium Compounds / toxicity*
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / chemistry
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Embryonic Development / drug effects
  • Eukaryotic Initiation Factor-4E / analysis
  • Eukaryotic Initiation Factor-4E / metabolism
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ovum / chemistry
  • Ovum / drug effects
  • Ovum / metabolism
  • Protein Binding
  • Sea Urchins / embryology
  • Sea Urchins / physiology
  • Time Factors

Substances

  • Chlorides
  • Chromium Compounds
  • Eukaryotic Initiation Factor-4E
  • Intracellular Signaling Peptides and Proteins
  • chromous chloride