Journal of Cancer Research and Clinical Oncology

, Volume 116, Issue 6, pp 609–614 | Cite as

Inhibition of protein phosphatases by microcystis and nodularin associated with hepatotoxicity

  • Shigeru Yoshizawa
  • Rie Matsushima
  • Mariyo F. Watanabe
  • Ken-ichi Harada
  • Akira Ichihara
  • Wayne W. Carmichael
  • Hirota Fujiki
Original Papers Experimental Oncology


Microcystins and nodularin, isolated from toxic blue-green algae, are hepatotoxic monocyclic polypeptides. Both microcystins and nodularin inhibited in vitro protein phosphatase activity present in a cytosolic fraction of mouse liver, bound to the okadaic acid receptors, protein phosphatases 1 and 2A, and thus resulted in the increase of phosphoproteins; this was referred to as the apparent “activation” of protein kinases. Their concentrations causing 50% of the maximal effects are comparable to that of okadaic acid, a potent protein phosphatase inhibitor and a potent tumor promoter, in the nanomolar range of concentration. The increase of phosphoproteins was observed in rat primary cultured hepatocytes and was subsequently associated with morphological changes, which appeared to be a step in the process of hepatotoxicity. The well-known hepatotoxic compounds,α-amanitin and phalloidin, did not show any effects similar to those of microcystins, nodularin and okadaic acid. It is suggested that the hepatotoxicity of microcystins and nodularin may result from inhibition of protein phosphatases and the increase of phosphoproteins.

Key words

Microcystin Nodularin Protein phosphatase 


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Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Shigeru Yoshizawa
    • 1
  • Rie Matsushima
    • 1
  • Mariyo F. Watanabe
    • 2
  • Ken-ichi Harada
    • 3
  • Akira Ichihara
    • 4
  • Wayne W. Carmichael
    • 5
  • Hirota Fujiki
    • 1
  1. 1.Cancer Prevention DivisionNational Cancer Center Research InstituteTokyoJapan
  2. 2.Tokyo Metropolitan Research Laboratory of Public HealthTokyoJapan
  3. 3.Faculty of PharmacyMeijo UniversityNagoyaJapan
  4. 4.Institute for Enzyme ResearchUniversity of TokushimaTokushimaJapan
  5. 5.Department of Biological SciencesWright State UniversityDaytonUSA

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