Mechanism of Action of Tetanus Toxin

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Abstract:

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.

Author(s):
Klempner, Mark S.
Author Organization(s):
TUFTS-NEW ENGLAND MEDICAL CENTER BOSTONMA
Descriptive Note:
Annual rept. 1 Sep 87-14 Mar 89; Final 1 Sep 85-14 Mar 89
Pagination:
0012

Security Markings

DOCUMENT & CONTEXTUAL SUMMARY

Distribution:
Approved For Public Release

RECORD

Collection: TR
Identifying Numbers
Contract/Grant Number(s):
DAMD17-85-C-5280
Task Number(s):
AA
Project Number(s):
3M161102BS12
Monitor Series:
USAMRDC
 Subject Terms
Joint Capability Areas:
JCA_1.3_Human Capital Management; JCA_1_Force Support; JCA_1.3.2_Personnel Management; JCA_1.2.7_Experimentation; JCA_1.2.5_Lessons Learned
Communities of Interest:
No COI(s) Identified
Descriptor(s):
*CALCIUM, *BACTERIAL TOXINS, *CELL STRUCTURE, *TETANUS, CATIONS, STIMULATION(PHYSIOLOGY), TOXICITY, PROTEINS, SUBSTRATES, TRANSPORT PROPERTIES, PURIFICATION, INHIBITORS, MONOCLONAL ANTIBODIES, BOVINES, PHOSPHATES, CYTOCHEMISTRY, HOMEOSTASIS, PHAGOCYTES, HYDROLASES, ADENOSINE PHOSPHATES, ADRENAL GLANDS, MITOCHONDRIA
Field(s)/Group(s):
Biochemistry, Toxicology
Keyword(s):
ADENOSINE TRIPHOSPHATE, ADENOSINE TRIPHOSPHATE PHOSPHOHYDROLASE, PHOSPHOHYDROLASES, LYSOSOMES, PE61102A, WU120, ASS12
Report Date:
1989 Jun 15