IndraLab
Statements
reach
"The acute sensitization initiated by optical stimulation (10 Hz) of TRPV1-ChR2 neurons, is sufficient to increase USP5 expression, which results in increased Cav3.2 T-type activity and increased mechanical hypersensitivity that is dependent on the interaction of USP5 and Cav3.2 [104]."
sparser
"No significant effects on current amplitude or biophysical properties of the channel were observed (7±2% inhibition (n=3) and 3±1% inhibition (n=3) of channel activity for suramin and gossypetin, respectively, which is indistinguishable from rundown), consistent with an action on the USP5-Cav3.2 channel interaction rather than direct effects on Cav3.2 channel function."
reach
"It is interesting that in a preliminary in vitro screen of potential mediators, which included brain-derived neurotrophic factor, nerve growth factor, and tumor necrosis factor-alpha, none were as effective as IL-1β at inducing interactions between USP5 and Cav3.2 (data not shown)."
sparser
"Consistent with our observations, this region has been previously described as a potential site for substrate targeting and specificity. xref In contrast, this region does not appear to be important for substrate modification by the catalytic site because deletion of the cUBP (163–291) domain did not affect the hydrolysis rate of ubiquitin-AMC. xref Together with our previous identification of a short (∼20 amino acid) stretch of residues in the domain III-IV linker of the Cav3.2 channel, xref we now have two complementary tools that allow us to disrupt USP5-Cav3.2 interactions both in vitro and in vivo."
sparser
"It is interesting that in a preliminary in vitro screen of potential mediators, which included brain-derived neurotrophic factor, nerve growth factor, and tumor necrosis factor-alpha, none were as effective as IL-1β at inducing interactions between USP5 and Cav3.2 (data not shown)."
sparser
"We have previously reported that pain hypersensitivity in diabetic ob/ob mice can be reversed by blocking the interactions between USP5 and Cav3.2 by small organic molecule mimetics. xref To determine whether the TAT-cUBP1-USP5 peptide was similarly effective, we assessed thermal withdrawal threshold in ob/ob mice before and after delivery of the TAT-cUBP1-USP5 peptide."
reach
"Using an intrathecal injection of a permeant peptide which impairs the interaction between USP5 and CaV3.2, several studies showed that it was possible to relieve rapidly (in a few minutes) pain sensation related to mechanical or thermal hypersensitivity.As a conclusion, many approaches using permeant peptides but also nonpeptidic synthetic molecules [42,43] have managed to alter the interaction between voltage-dependent calcium channel partners in order to successfully reverse various symptoms associated with different pathologies."
sparser
"The acute sensitization initiated by optical stimulation (10 Hz) of TRPV1-ChR2 neurons, is sufficient to increase USP5 expression, which results in increased Cav3.2 T-type activity and increased mechanical hypersensitivity that is dependent on the interaction of USP5 and Cav3.2 [ xref ]."
sparser
"While the above findings support the hypothesis that IL-1β drives upregulation of T-type channels via USP5 to induce pain, these effects were studied under acute conditions (<1 h) that yield transient pain (∼15 min) and may be secondary to interactions between IL-1β and glial cells, which are known to express IL-1RI. xref , xref To study neuroinflammatory interaction more directly, while reflecting sustained release after physical injury, we used DRG neuron cultures to evaluate the level of USP5 bound to Cav3.2 in response to overnight (∼24 h) exposure to IL-1β."
sparser
"Under these conditions and relative to vehicle control (0.1% BSA in PBS), IL-1β produced a clear increase in the level of interaction between USP5 and Cav3.2 channels in co-IP experiments ( xref and ( xref )), which is mediated by IL-1RI, as this effect was almost completely attenuated in the presence of IL-1Ra (100 ng/ml)."
sparser
"Since this process is relevant to both inflammatory and neuropathic pain states, xref , xref we initially proposed that neural activity may be a common trigger. xref This idea was supported by observations that activity stemming from optogenetically targeted cutaneous nociceptors alone is sufficient to upregulate USP5 expression, and therefore to increase interactions between USP5 and Cav3.2. xref However, this activity-dependent phenomenon is not self-sustaining, instead promoting only a transient pain state that cannot account for the upregulation observed after injury."