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Mar. Drugs 2015, 13(10), 6505-6520; doi:10.3390/md13106505

Cell Death Inducing Microbial Protein Phosphatase Inhibitors—Mechanisms of Action

1
Department of Biomedicine, University of Bergen, Jonas Lies vei 81, N-5009 Bergen, Norway
2
Department of Clinical Science, University of Bergen, Jonas Lies vei 65, N-5021 Bergen, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Received: 11 September 2015 / Revised: 12 October 2015 / Accepted: 15 October 2015 / Published: 22 October 2015
View Full-Text   |   Download PDF [357 KB, uploaded 22 October 2015]   |  

Abstract

Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms believed to be responsible for the death induction and tumor promotion with focus on the interdependent production of reactive oxygen species (ROS) and activation of Ca2+/calmodulin kinase II (CaM-KII). New data are presented using inhibitors of specific ROS producing enzymes to curb nodularin/MC-induced liver cell (hepatocyte) death. They indicate that enzymes of the arachidonic acid pathway, notably phospholipase A2, 5-lipoxygenase, and cyclooxygenases, may be required for nodularin/MC-induced (and presumably OA-induced) cell death, suggesting new ways to overcome at least some aspects of OA and MC toxicity. View Full-Text
Keywords: microcystin; okadaic acid; nodularin; cell death; apoptosis; protein phosphatase; inhibitor microcystin; okadaic acid; nodularin; cell death; apoptosis; protein phosphatase; inhibitor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kleppe, R.; Herfindal, L.; Døskeland, S.O. Cell Death Inducing Microbial Protein Phosphatase Inhibitors—Mechanisms of Action. Mar. Drugs 2015, 13, 6505-6520.

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