Geigerin-induced disorganization of desmin, an intermediate filament of the cytoskeleton, in a murine myoblast cell line (C2C12)

Ingestion of large quantities of Geigeria species by sheep causes vermeersiekte, an economically important poisoning in southern Africa. The toxic principles are several sesquiterpene lactones, such as vermeerin, geigerin and ivalin. These sesquitepene lactones are myotoxic and the disease is characterized by microscopic and ultrastructural lesions in skeletal and cardiac muscle. Murine myoblast cells (C2C12) were exposed to 2.0, 2.5 and 5.0 mM geigerin for 24, 48 and 72 h to evaluate its effect on cytoskeletal proteins and filaments using immunocytochemistry and immunofluorescence staining. A concentration-dependent cytotoxic response was observed in desmin-expressing murine myoblasts under the light microscope, evidenced by disorganization and dot-like perinuclear aggregation of desmin filaments in the cells. beta-Tubulin, other desmin-associated proteins (alpha B-crystallin and synemin) as well as the microfilament F-actin were unaffected. The disorganization and aggregation of desmin following exposure to increasing geigerin concentrations is significant and can explain some of the striated muscle lesions observed in vermeersiekte.