Calore_1999_Ecotoxicol.Environ.Saf_43_187

The degenerative process of the myofibers of the diaphragm of rats intoxicated with the organophosphate isofenphos, a compound that inhibits esterases, was studied at different intervals of intoxication. Early disorganization of the intermyofibrillar network and of the myofilaments, as well as dilatation of organelles, were observed by use of transmission electron microscopy. These changes precede macrophage invasion of the muscle fibers. Early expression of ubiquitin was observed in segments of muscle fibers by immunohistochemistry. Bands of polyubiquitin complexes in muscle homogenates were observed by immunoblotting. These bands disappeared in later stages of intoxication. A 42.5-kDa band corresponds to actin, as observed by immunoblotting using antisarcometric actin. This indicates relatively large amounts of polyubiquitin complex associated with sarcomeric actin in muscle fibers in early stages of intoxication. Based on these results it seems that actin is an important target in organophosphate-induced myofiber degradation and that the degradation of this protein-by the polyubiquitin pathway-may play an important role in the early disorganization of the sarcomere, as observed by electron microscopy. A possible role of the ubiquitin proteolytic pathway is that of trying to eliminate proteins modified in the early phases of muscle fiber degeneration, which is a necessary step for regeneration of the posterior segmental muscle.