Rapid microfilament reorganization induced in isolated rat hepatocytes by microcystin-LR, a cyclic peptide toxin

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Eriksson, Paatero, Meriluoto, Codd, Kass, Nicotera, Orrenius
Publiceringsår: 1989
Tidskrift: Experimental Cell Research
Tidskriftsakronym: Exp Cell Res
Volym: 185
Nummer: 1
Artikelns första sida, sidnummer: 86
Artikelns sista sida, sidnummer: 100
ISSN: 0014-4827
eISSN: 1090-2422


Abstrakt

The cyclic heptapeptide hepatotoxin microcystin-LR from the cyanobacterium Microcystis aeruginosa induces rapid and characteristic deformation of isolated rat hepatocytes. We investigated the mechanism(s) responsible for cell shape changes (blebbing). Our results show that the onset of blebbing was accompanied neither by alteration in intracellular thiol and Ca2+ homeostasis nor by ATP depletion. The irreversible effects were insensitive to protease and phospholipase inhibitors and also to thiol-reducing agents, excluding the involvement of enhanced proteolysis, phospholipid hydrolysis, and thiol modification in microcystin-induced blebbing. In contrast, the cell shape changes were associated with a remarkable reorganization of microfilaments as visualized both by electron microscopy and by fluorescent staining of actin with rhodamine-conjugated phalloidin. The morphological effects and the microfilament reorganization were specific for microcystin-LR and could not be induced by the microfilament-modifying drugs cytochalasin D or phalloidin. Using inhibition of deoxyribonuclease I as an assay for monomeric actin, we found that the microcystin-induced reorganization of hepatocyte microfilaments was not due to actin polymerization. On the basis of the rapid microfilament reorganization and the specificity of the effects, it is suggested that microcystin-LR constitutes a novel microfilament-perturbing drug with features that are clearly different from those of cytochalasin D and phalloidin.

Senast uppdaterad 2019-24-10 vid 03:14