Microcystin-LR causes the collapse of actin filaments in primary human hepatocytes.
Microcystin-LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A and causes alterations in cytoskeletal filaments and morphological changes that underlie apoptosis in rat hepatocytes. It has also been reported that it caused several cases of human deaths and illness. As no study on the effect of microcystins on human hepatocytes was done, yet, the aim of the study is to evaluate the toxicity of MCLR on primary human hepatocytes. The hepatocytes were incubated in 12.5-50 nM MCLR for 3, 6 and 9 h, fixed and stained with fluorescent probes for actin filaments and nuclei. Spectral laser-scanning confocal microscopy revealed that in the MCLR-treated primary human hepatocytes the actin mesh collapsed into the center of the cell, similarly as it has been described for rat hepatocytes. Cells were blebbing, fragmenting, and separated from each other. The nuclei in the affected cells condensed. In conclusion, this study confirms that MCLR is toxic to primary human hepatocytes, and it may be responsible for the liver failure cases observed after acute cyanobacterial poisoning.
Batista
Tina
T
Institute of Pathophysiology, School of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia.
de Sousa
Georges
G
Suput
Jerneja Strupi
JS
Rahmani
Roger
R
Suput
Dusan
D
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D005456:Fluorescent Dyes; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008387:Marine Toxins; D052998:Microcystins; D018613:Microscopy, Confocal; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005456:Fluorescent Dyes; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR