PMID- 29906413
OWN - NLM
STAT- MEDLINE
DCOM- 20190213
LR  - 20190215
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 138
DP  - 2018 Aug
TI  - A SNAP-25 cleaving chimera of botulinum neurotoxin /A and /E prevents 
      TNFalpha-induced elevation of the activities of native TRP channels on early 
      postnatal rat dorsal root ganglion neurons.
PG  - 257-266
LID - S0028-3908(18)30295-8 [pii]
LID - 10.1016/j.neuropharm.2018.06.016 [doi]
AB  - Transient receptor potential (TRP) vallinoid 1 (TRPV1) and ankyrin 1 (TRPA1) are 
      two transducing channels expressed on peripheral sensory nerves involved in pain 
      sensation. Upregulation of their expression, stimulated by inflammatory cytokines 
      and growth factors in animal pain models, correlate with the induction of 
      nociceptive hyper-sensitivity. Herein, we firstly demonstrate by 
      immuno-cytochemical labelling that TNFalpha augments the surface content of these 
      channels on rat cultured dorsal root ganglion (DRG) neurons which, in turn, 
      enhances the electrophysiological and functional responses of the latter to their 
      specific agonists. A molecular basis underlying this TNFalpha-dependent enhancement 
      was unveiled by pre-treating DRGs with a recently-published chimeric protein, 
      consisting of the protease light chain (LC) of botulinum neurotoxin (BoNT) 
      serotype E fused to full-length BoNT/A (LC/E-BoNT/A). This cleaves 
      synaptosomal-associated protein of Mr 25k (SNAP-25) and reported previously to 
      exhibit anti-nociceptive activity in a rat model of neuropathic pain. Low pM 
      concentrations of this chimera were found to prevent the TNFalpha-stimulated delivery 
      of TRPV1/A1 to the neuronal plasmalemma and, accordingly, decreased their 
      incremental functional activities relative to those of control cells, an effect 
      accompanied by SNAP-25 cleavage. Advantageously, LC/E-BoNT/A did not reduce the 
      basal surface contents of the two channels or their pharmacological responses. 
      Thus, use of multiple complementary methodologies provides evidence that 
      LC/E-BoNT/A abolishes the TNFalpha-dependent augmented, but not resting, surface 
      trafficking of TRPV1/A1. As TNFalpha is known to induce nociceptive hyper-sensitivity 
      in vivo, our observed inhibition by LC/E-BoNT/A of its action in vitro could 
      contribute to its potential alleviation of pain.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Nugent, Marc
AU  - Nugent M
AD  - International Centre for Neurotherapeutics, Dublin City University, Glasnevin, 
      Dublin 9, Ireland.
FAU - Yusef, Yamil R
AU  - Yusef YR
AD  - International Centre for Neurotherapeutics, Dublin City University, Glasnevin, 
      Dublin 9, Ireland.
FAU - Meng, Jianghui
AU  - Meng J
AD  - International Centre for Neurotherapeutics, Dublin City University, Glasnevin, 
      Dublin 9, Ireland.
FAU - Wang, Jiafu
AU  - Wang J
AD  - International Centre for Neurotherapeutics, Dublin City University, Glasnevin, 
      Dublin 9, Ireland.
FAU - Dolly, J Oliver
AU  - Dolly JO
AD  - International Centre for Neurotherapeutics, Dublin City University, Glasnevin, 
      Dublin 9, Ireland. Electronic address: oliver.dolly@dcu.ie.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180612
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Sensory System Agents)
RN  - 0 (Snap25 protein, rat)
RN  - 0 (Synaptosomal-Associated Protein 25)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.69 (Botulinum Toxins)
RN  - EC 3.4.24.69 (Botulinum Toxins, Type A)
RN  - S07O44R1ZM (Capsaicin)
RN  - SY7Q814VUP (Calcium)
RN  - T579M564JY (botulinum toxin type E)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Botulinum Toxins/*pharmacology
MH  - Botulinum Toxins, Type A/*pharmacology
MH  - Calcium/metabolism
MH  - Capsaicin/pharmacology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Escherichia coli
MH  - Ganglia, Spinal/*drug effects/metabolism
MH  - Rats, Sprague-Dawley
MH  - Sensory Receptor Cells/drug effects/metabolism
MH  - Sensory System Agents/*pharmacology
MH  - Synaptosomal-Associated Protein 25/metabolism
MH  - TRPV Cation Channels/agonists/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
OTO - NOTNLM
OT  - Botulinum neurotoxin
OT  - SNAP-25
OT  - TNFalpha
OT  - TRPA1
OT  - TRPV1
EDAT- 2018/06/16 06:00
MHDA- 2019/02/14 06:00
CRDT- 2018/06/16 06:00
PHST- 2017/12/23 00:00 [received]
PHST- 2018/05/29 00:00 [revised]
PHST- 2018/06/11 00:00 [accepted]
PHST- 2018/06/16 06:00 [pubmed]
PHST- 2019/02/14 06:00 [medline]
PHST- 2018/06/16 06:00 [entrez]
AID - S0028-3908(18)30295-8 [pii]
AID - 10.1016/j.neuropharm.2018.06.016 [doi]
PST - ppublish
SO  - Neuropharmacology. 2018 Aug;138:257-266. doi: 10.1016/j.neuropharm.2018.06.016. 
      Epub 2018 Jun 12.