Linked Life Data

21094256

Source:http://linkedlifedata.com/resource/pubmed/id/21094256

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-24
pubmed:abstractText
The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition reactions we sought to further elucidate the mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium signalling was used to determine the mechanism of activation of TRPA1 expressed in HEK293 cells with a series of related compounds which were capable of either direct and/or conjugate addition processes. These results were confirmed using physiological recordings with isolated vagus nerve preparations. We found negligible channel activation with chemicals which could only react with cysteine residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic acid. Compounds able to react via either conjugate or direct addition, such as acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester, cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration dependent manner as did compounds only capable of direct addition, namely propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For molecules capable of direct or conjugate additions, the results suggest for the first time that TRPA1 may be activated preferentially by direct addition of the thiol group of TRPA1 cysteines to the agonist carbonyl carbon of ?,?-unsaturated carbonyl-containing compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1096-1186
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30-6
pubmed:meshHeading
pubmed-meshheading:21094256-Acrylates, pubmed-meshheading:21094256-Animals, pubmed-meshheading:21094256-Calcium Channels, pubmed-meshheading:21094256-Calcium Signaling, pubmed-meshheading:21094256-Cinnamates, pubmed-meshheading:21094256-Cysteine, pubmed-meshheading:21094256-Dose-Response Relationship, Drug, pubmed-meshheading:21094256-Esters, pubmed-meshheading:21094256-Guinea Pigs, pubmed-meshheading:21094256-HEK293 Cells, pubmed-meshheading:21094256-Humans, pubmed-meshheading:21094256-Magnetic Resonance Spectroscopy, pubmed-meshheading:21094256-Male, pubmed-meshheading:21094256-Membrane Potentials, pubmed-meshheading:21094256-Molecular Structure, pubmed-meshheading:21094256-Nerve Tissue Proteins, pubmed-meshheading:21094256-Structure-Activity Relationship, pubmed-meshheading:21094256-TRPV Cation Channels, pubmed-meshheading:21094256-Time Factors, pubmed-meshheading:21094256-Transfection, pubmed-meshheading:21094256-Transient Receptor Potential Channels, pubmed-meshheading:21094256-Vagus Nerve
pubmed:year
2011
pubmed:articleTitle
TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids.
pubmed:affiliation
Cardiovascular and Respiratory Studies, The University of Hull, Castle Hill Hospital, Cottingham, Hull HU16 5JQ, UK. L.R.Sadofsky@Hull.ac.uk
pubmed:publicationType
Journal Article, In Vitro