Effects of cobalt on haem proteins of erythropoietin-producing HepG2 cells in multicellular spheroid culture

FEBS Lett. 1994 Jul 11;348(2):216-8. doi: 10.1016/0014-5793(94)00607-5.


The hypoxia-induced increase of spectrophotometrically measured light absorption at 560 nm, considered as reduced cytochrome b, in HepG2 cells is diminished after exposure to cobalt chloride (50 or 100 microM) for 18-36 h. The redox state of cytochrome c and cytochrome aa3, however, remains stable, indicating a particular affinity of cytochrome b for cobalt. Erythropoietin production of HepG2 cells increases after application of cobalt chloride, whereas H2O2 production, as measured by the dihydrorhodamine technique, decreases. It is concluded that cobalt stimulates a signal cascade with cytochrome b as receptor and H2O2 as second messenger for regulating erythropoietin production.

MeSH terms

  • Cells, Cultured
  • Cobalt / pharmacology*
  • Cytochromes / drug effects*
  • Cytochromes / metabolism
  • Erythropoietin / biosynthesis*
  • Hydrogen Peroxide / metabolism
  • Oxidation-Reduction
  • Signal Transduction


  • Cytochromes
  • Erythropoietin
  • Cobalt
  • Hydrogen Peroxide
  • cobaltous chloride