Mechanism of Action of Tetanus Toxin
Annual rept. 1 Sep 87-14 Mar 89; Final 1 Sep 85-14 Mar 89
TUFTS-NEW ENGLAND MEDICAL CENTER BOSTONMA
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We have previously reported that tetanus toxin TT increased ATP- dependent Calcium uptake by human neutrophil lysosomes, and we hypothesized that the toxin activates the Ca ATPase present in these organelles. However, we have been unable to show any phosphorylating effect of TT on any lysosomal protein. In subsequent experiments, using mitochondrial inhibitors and a mitochondrial substrate, we showed that the stimulation of ATP-dependent Ca uptake is an effect of TT on mitochondria. We confirmed this finding by using purified bovine adrenal mitochondria. However, we were then unable to show any specificity for the TT action by using TT-specific ganglioside affinity chromatography, as well as immunoabsorption with monoclonal antibodies. We conclude that the described TT effect was due to the presence of phosphate salts in the TT preparation which facilitated Ca transport by mitochondria. Keywords Calcium homeostasis, Macrophages, Lysosomes.