Microcystin-LR and okadaic acid-induced cellular effects: a dualistic response

This review summarises the existing data on the molecular e¡ects of microcystin-LR inhibition of PP1 and PP2A both in vivo and in vitro, and where possible, compares this to the action of okadaic acid. ß 2003 Federation of European Biochemical Societies

Michelle M Gehringer


Scholarcy highlights

  • Microcystin-LR is a cyclic heptapeptide toxin produced by several genera of cyanobacteria
  • As lipid peroxidation is a good indicator of oxidative stress in cells, the authors concluded that chronic exposure to sublethal doses of MCLR resulted in oxidative stress and suggested that it may play an important role in the chronic liver damage induced by MCLR toxicosis at sublethal levels
  • Whether the hepatocyte undergoes apoptosis or increased cellular proliferation appears to be dependent on the e¡ective concentration of toxin to which it is exposed as demonstrated in vitro
  • Oxidative stress is a known stimulus of mitogen-activated protein kinases and H2O2 can induce the activity of Jun-activating kinase
  • Either or both of these mechanisms could induce hepatic damage leading to necrosis/apoptosis and/or increased cellular proliferation
  • The extent of injury in vivo is in turn dependent on the level of exposure to the toxin, e⁄ciency of uptake and the detoxi¢cation process within the liver to remove both MC and MCLR-induced reactive oxygen species
  • In vivo studies indicate a clear role for MCLR to act as a tumour promoter at dose levels in the range of 1^10 Wg/kg i.p. or 382^693 Wg/kg orally, being associated with the development of liver, skin and possibly colon cancer

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