Inhibitory effect of polysulfide, an endogenous sulfur compound, on oxidative stress-induced TRPA1 activation.
Neurosci Lett
; 757: 135982, 2021 07 13.
Article
em En
| MEDLINE
| ID: mdl-34023406
ABSTRACT
Polysulfide (PS), an endogenous sulfur compound, generated by oxidation of hydrogen sulfide, has a stimulatory action on the nociceptive TRPA1 channel. TRPA1 is also activated by reactive oxygen species such as hydrogen peroxide (H2O2) produced during inflammation. Here, we examined the effect of PS on H2O2-induced responses in native and heterologously expressed TRPA1 using a cell-based calcium assay. We also carried out behavioral experiments in vivo. In mouse sensory neurons, H2O2 elicited early TRPA1-dependent and late TRPA1-independent increases of [Ca2+]i. The former was suppressed by the pretreatment with PS. In cells heterologously expressed TRPA1, PS suppressed [Ca2+]i responses to H2O2. Simultaneous measurement of [Ca2+]i and the intracellular PS level revealed that scavenging effect of PS was not related to the inhibitory effect. Removal of extracellular Ca2+, a calmodulin inhibitor and dithiothreitol attenuated the inhibitory effect of PS. Pretreatment with PS diminished nociceptive behaviors induced by H2O2. The present data suggest that PS suppresses oxidative stress-induced TRPA1 activation due to cysteine modification and Ca2+/calmodulin signaling. Thus, endogenous sulfurs may have regulatory roles in nociception via functional changes in TRPA1 under inflammatory conditions.
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Base de dados:
MEDLINE
Assunto principal:
Sulfetos
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Nociceptividade
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Canal de Cátion TRPA1
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Analgésicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article