10.5061/DRYAD.X3FFBG7H1
Mo, Xiaoyi
Wuhan University
Liu, Qiang
Wuhan University
Gao, Luna
Wuhan University
Xie, Chang
Wuhan University
Wei, Xin
Wuhan University
Pang, Peiyuan
Wuhan University
Tian, Quan
Wuhan University
Gao, Yue
Wuhan University
Zhang, Youjing
Wuhan University
Wang, Yuanyuan
Wuhan University
Xiong, Tianchen
Wuhan University
Zhong, Bo
Wuhan University
Li, Dongdong
0000-0002-6731-4771
Inserm
Yao, Jing
Wuhan University
The industrial solvent 1,4-Dioxane causes hyperalgesia by targeting
capsaicin receptor TRPV1
Dryad
dataset
2020
FOS: Biological sciences
2022-01-03T00:00:00Z
2022-01-03T00:00:00Z
en
https://doi.org/10.1186/s12915-021-01211-0
573142 bytes
11
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Background: The synthetic chemical 1,4-dioxane is used as industrial
solvent, food and care product additive. 1,4-Dioxane has been noted to
influence the nervous system in long-term animal experiments and in
humans, but the molecular mechanisms underlying its effects on animals
were not previously known. Results: Here, we report that 1,4-dioxane
potentiates the capsaicin-sensitive transient receptor potential (TRP)
channel TRPV1, thereby causing hyperalgesia in mouse model. This effect
was abolished by CRISPR/Cas9-mediated genetic deletion of TRPV1 in sensory
neurons, but enhanced under inflammatory conditions. 1,4-Dioxane lowered
the temperature threshold for TRPV1 thermal activation and potentiated the
channel sensitivity to agonistic stimuli. 1,3-dioxane and tetrahydrofuran
which are structurally related to 1,4-dioxane also potentiated TRPV1
activation. The residue M572 in the S4-S5 linker region of TRPV1 was found
to be crucial for direct activation of the channel by 1,4-dioxane and its
analogues. A single residue mutation M572V abrogated the
1,4-dioxane-evoked currents while largely preserving the capsaicin
responses. Our results further demonstrate that this residue exerts a
gating effect through hydrophobic interactions and support the existence
of discrete domains for multimodal gating of TRPV1 channel. Conclusions:
Our results suggest TRPV1 is a co-receptor for 1,4-dioxane, and that this
accounts for its ability to dysregulate body nociceptive sensation.
Electrophysiological data were mainly collected from traditional
patch-clamp recordings and Ca2+ imaging. All behavioral experiments with
mice were conducted in a double-blind manner. Paw-withdrawal latency of
thermal or mechanical hyperalgesia was determined by a
temperature-controlled Plantar Test Instrument and von Frey apparatus,
respectively.
This dataset contains nine excel sheets including all data used to analyze
the effect of the industrial solvent 1,4-Dioxane on thermal TRPV1 channel.
Each excel sheet corresponds to a figure, and all statistical results
along with the statistical methods are exhibited in the excel sheet. 1)
Fig1-1,4-Dioxane ms figsupplement data Data used for Figure 1 ‘1,4-Dioxane
causes mice hyperalgesia via TRPV1 activation’. (1) Experimental data from
mice obtained using the Radiant Heat and Von Frey assay and was
illustrated in Fig 1a&b. (2) Data collected for paw volume
examination and was shown in Fig 1c. (3) Ca2+ imaging data and
electrophysiological data obtained in acutely dissociated DRG and TG
neurons from Trpv1+/+ and Trpv1-/- mice and were demonstrated in Fig 1d-m.
2) Fig2-1,4-Dioxane ms figsupplement data Electrophysiological data were
collected from TRPV1-expressing HEK293 cells by single-channel recordings
or whole-cell recordings and were used to illustrate the gating and
modulation of TRPV1 channels by 1,4-dioxane as shown in Figure 2. 3)
Fig3-1,4-Dioxane ms figsupplement data This data set was obtained from
TRPV1-expressing HEK293 cells stimulated by heat and was used to analyze
the current amplitudes and normalized responses as illustrated in Figure
3. 4) Fig4-1,4-Dioxane ms figsupplement data Data were collected to
analyze the activation of TRPV1 under inflammation-related conditions in
Figure 4. Electrophysiological data were obtained and analyzed for Figure
4a-f. Behavior data shown in Figure 4g were collected from mice under
carrageenan-induced inflammation conditions using the Radiant Heat and Von
Frey assay. 5) Fig5-1,4-Dioxane ms figsupplement data Electrophysiological
data obtained by whole-cell recordings in HEK293 cells were used for
Figure 5 to demonstrate the residue M572 within the S4-S5 linker region of
TRPV1 mediates the effect of 1,4-dioxane and its analogues. 6)
Fig6-1,4-Dioxane ms figsupplement data Electrophysiological data were
collected for Figure 6. Whole-cell recordings were performed in HEK 293
cells transiently transfected with individual mutation. 7)
FigS1-1,4-Dioxane ms figsupplement data Electrophysiological data were
collected for Figure S1 to show effects of 1,4-dioxane on variable TRP
channels. 8) FigS3-1,4-Dioxane ms figsupplement data Electrophysiological
data were obtained for Figure S3 to illustrate the amplitude of TRPV1
single-channel currents elicited by different conditions. 9)
FigS4-1,4-Dioxane ms figsupplement data Electrophysiological data were
collected for Figure S4 to exhibit the inhibitory effect of ruthenium red
(RR) on TRPV1 currents.