Critical role of reactive oxygen species formation in microcystin-induced cytoskeleton disruption in primary cultured hepatocytes.
Cyanobacteria (blue-green algae)-contaminated water is a worldwide public health problem. Microcystins are a group of liver-specific toxins generated by cyanobacteria. It is generally believed that the protein phosphorylation that leads to the disruption of intermediate filaments plays an important role in microcystin-induced hepatotoxicity. However, the mechanisms that contribute to the microcystin-induced alterations of microtubules and microfilaments are not fully understood. In the present study, the effects of microcystin-fR (M-LR), the most common microcystin, were examined on the organization of cellular microtubules and microfilaments in primary cultured rat hepatocytes. Our results indicate that M-LR initiated reactive oxygen species (ROS) formation followed by altering the cytoskeleton structures, which eventually led to significant LDH leakage. These effects were completely prevented by TEMPOL, a superoxide dismutase mimic, and also partially prevented by desferoxamine. These findings provide further evidence that ROS formation, especially superoxide radical, plays a crucial role in M-LR-induced disruption of cytoskeleton organization and consequent hepatotoxicity.
Ding
W X
WX
Center for Environmental and Occupational Health, Department of Community, Occupational, and Family Medicine, National University of Singapore, Singapore.
Shen
H M
HM
Ong
C N
CN
D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D000458:Cyanobacteria; D003599:Cytoskeleton / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000648:ultrastructure; D008099:Liver / Q000166:cytology / Q000187:drug effects; D052998:Microcystins; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014873:Water Pollutants / Q000633:toxicity*
D001427:Bacterial Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D017382:Reactive Oxygen Species; D014873:Water Pollutants; C078588:microcystin