Alkylated metal compounds mimic signal molecules: the induction of programmed cell death via membrane receptors
Harald Friedrich Krug, Klohn P.-C., Martin Göttlicher, Peter A. Herrlich · 2001
Organometal compounds are widely used chemicals. They can be found in antifouling paint, wood preservatives and they were utilised for chemical syntheses. Moreover, trialkylated tin is a contaminant in plastics. Tributyltin (TBT) causes severe toxicity in mammals like thymus atrophy and immunosuppression, in vitro it induces apoptosis very potently (1). Nevertheless, the mechanism of cytotoxicity is obscure. We could demonstrate that TBT induces cell death in a variety of cell lines by triggering the intracellular signalling cascade via membrane receptors leading to apoptosis. This effect appears already at concentrations as low as 100 nM up to 2 öM, depending on the cell type and the incubation time. Exposure of phosphatidylserine on the surface of apoptotic cells is a caspase-dependent process and frequently used as apoptotic endpoint. TBT induced a rapid exposure of phosphatidylserine as determined by Annexin V binding and this early onset of apoptosis could be prevented completely in a BJAB cell line (BJAB-FADD-dn) which overexpressed the dominant-negative form of FADD,