Cell Death Inducing Microbial Protein Phosphatase Inhibitors—Mechanisms of Action

Marine Drugs

Rune Kleppe¹  Lars Herfindal¹  Stein Ove Døskeland¹ 

[1] Department of Biomedicine, University of Bergen, Jonas Lies vei 81, N-5009 Bergen, Norway; E-Mails:

关键词: microcystin;    okadaic acid;    nodularin;    cell death;    apoptosis;    protein phosphatase;    inhibitor;   

DOI  :  10.3390/md13106505

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.