Toosendanin interferes with pore formation of botulinum toxin type A in PC12 cell membrane
Abstract
Aim: Botulinum neurotoxins (BoNT) abort the process of neurotransmitter release
at presynaptic motor nerve terminals, causing muscle paralysis. The ability
of botulinum toxin to produce its effect is dependent on the ability of the light
chain to cleave the SNARE proteins associated with transmitter release. Translocation
of the light chain protease through the heavy chain-formed channel is a
pivotal step in the intoxication process. Toosendanin (TSN), a triterpenoid derivative
extracted from a Chinese traditional medicine, has been demonstrated to
be an effective cure for experimental botulism. This study was designed to explore
the antibotulismic mechanisms of toosendanin. Methods: The inside-out singlechannel
recording patch-clamp technique was used to record the BoNT/A-induced
currents in the presence and absence of TSN. Results: Channel formation
was delayed and the sizes of the channels were reduced in the TSN-treated PC12
cell membrane. Conclusion: The antibotulismic effect of TSN might occur via
interference with toxin translocation.
Keywords:
at presynaptic motor nerve terminals, causing muscle paralysis. The ability
of botulinum toxin to produce its effect is dependent on the ability of the light
chain to cleave the SNARE proteins associated with transmitter release. Translocation
of the light chain protease through the heavy chain-formed channel is a
pivotal step in the intoxication process. Toosendanin (TSN), a triterpenoid derivative
extracted from a Chinese traditional medicine, has been demonstrated to
be an effective cure for experimental botulism. This study was designed to explore
the antibotulismic mechanisms of toosendanin. Methods: The inside-out singlechannel
recording patch-clamp technique was used to record the BoNT/A-induced
currents in the presence and absence of TSN. Results: Channel formation
was delayed and the sizes of the channels were reduced in the TSN-treated PC12
cell membrane. Conclusion: The antibotulismic effect of TSN might occur via
interference with toxin translocation.