CRITICAL ROLE OF REACTIVE OXYGEN SPECIES FORMATION IN MICROCYSTIN-INDUCED CYTOSKELETON DISRUPTION IN PRIMARY CULTURED HEPATOCYTES

Abstract

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-LR (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.