PARAQUAT INDUCES ACTIN ASSEMBLY IN DEPOLYMERIZING CONDITIONS

The molecular mechanism (or mechanisms) at the basis of paraquat (PQ) (a widely used herbicide) toxicity is far from being fully understood, Until now, two main points of view have emerged: 1) PQ-related cell i njuries could be mediated by toxic oxygen free radicals coming from th e metabolism of the herbicide by the microsomal enzyme system, and/or 2) PQ, by inducing mitochondrial swelling and breakage, could cause tr oubles in cell energy charge, then driving the cell to death, Recently , some of cytoskeletal structures (microtubules and microfilaments) ha ve been proposed as further PQ cell targets, The microfilament system in particular seems to be markedly affected by the herbicide, but so f ar no direct evidence associates PQ to actin damage, In this study, ex perimental data are presented concerning the direct effect of PQ on ac tin dynamics in solution, We demonstrate that actin selectively binds PQ; moreover, PQ induces the formation of actin sopramolecular structu res in depolymerizing medium (G-buffer), Furthermore, by the interacti ons with F-actin crosslinking proteins (alpha-actinin and filamin), FI TC-phalloidin, and myosin subfragment 1 (S1), it is demonstrated that PQ-induced actin aggregates are undoubtedly built up by F-actin, Elect ron micrographs showed that PQ-induced actin polymers are very short a nd tend to aggregate one to another, This mutual cohesion leads to the steric blockage of polymer growing ends as suggested by nucleated act in polymerization assays, Sonication, by releasing F-actin fragments f rom short polymer aggregates, allows actin polymer ends to regain thei r growing ability.-Milzani, A., DalleDonne, I., Vailati, G., Colombo, R. Paraquat induces actin assembly in depolymerizing conditions.