| Autor: |
Matthews, Christopher C., Fishman, Paul S., Parks, Deborah A., Patwardhan, Anil J. |
| Předmět: |
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| Zdroj: |
Natural Toxins; 1999, Vol. 7 Issue 4, p151, 0p |
| Abstrakt: |
The non-toxin 50 kD C-terminus peptide of the heavy chain of tetanusHc contains the ganglioside binding domain of tetanus toxin (TTX). Hc retains much of the capacity of tetanus toxinfor binding internalization and transport by neurons. For this reason tetanus Hc has been studied as a vector for delivery of therapeutic proteins to neurons. We directly compared Hc and TTX in the capacity to bind and be internalized by neurons by ELISA. Primary cultures of dissociated fetal cortical neurons were incubated with equimolar amounts of TTX or Hc. Neuronal associated tetanus protein was 4-8 fold greater on a molar basis with tetanustoxin compared to Hc (1 h incubation). This increase in neuronal tetanus protein was evident with incubation in concentrationsfrom 0.1 muM to 2 muM. There were greater amounts of TTX delivered to the cultured cells at both 0 deg. C (representing membrane bound tetanus protein) and 37 deg. C (bound and internalized tetanus protein). Unlike Hc, TTX showed significant continued accumulationof protein with increasing incubation durations. Neuronal associatedTTX increased 2-3 fold over incubation times ranging from 1 to 8 h. Tetanus toxin appears to be clearly superior to the ganglioside binding fragment (Hc) in the capacity for neuronal binding and internalization. Atoxic tetanus proteins containing additional molecular domains as well as Hc may be more suitable vectors forlinkage with therapeutic proteins and delivery to neurons. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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