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Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress.
J Neurosci. 2008 Mar 05; 28(10):2485-94.JN

Abstract

Transient receptor potential A1 (TRPA1) is expressed in a subset of nociceptive sensory neurons where it acts as a sensor for environmental irritants, including acrolein, and some pungent plant ingredients such as allyl isothiocyanate and cinnamaldehyde. These exogenous compounds activate TRPA1 by covalent modification of cysteine residues. We have used electrophysiological methods and measurements of intracellular calcium concentration ([Ca(2+)](i)) to show that TRPA1 is activated by several classes of endogenous thiol-reactive molecules. TRPA1 was activated by hydrogen peroxide (H(2)O(2); EC(50), 230 microM), by endogenously occurring alkenyl aldehydes (EC(50): 4-hydroxynonenal 19.9 microM, 4-oxo-nonenal 1.9 microM, 4-hydroxyhexenal 38.9 microM) and by the cyclopentenone prostaglandin, 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ(2), EC(50): 5.6 microM). The effect of H(2)O(2) was reversed by treatment with dithiothreitol indicating that H(2)O(2) acts by promoting the formation of disulfide bonds whereas the actions of the alkenyl aldehydes and 15d-PGJ(2) were not reversed, suggesting that these agents form Michael adducts. H(2)O(2) and the naturally occurring alkenyl aldehydes and 15d-PGJ(2) acted on a subset of isolated rat and mouse sensory neurons [approximately 25% of rat dorsal root ganglion (DRG) and approximately 50% of nodose ganglion neurons] to evoke a depolarizing inward current and an increase in [Ca(2+)](i) in TRPA1 expressing neurons. The abilities of H(2)O(2), alkenyl aldehydes and 15d-PGJ(2) to raise [Ca(2+)](i) in mouse DRG neurons were greatly reduced in neurons from trpa1(-/-) mice. Furthermore, intraplantar injection of either H(2)O(2) or 15d-PGJ2 evoked a nocifensive/pain response in wild-type mice, but not in trpa1(-/-) mice. These data demonstrate that multiple agents produced during episodes of oxidative stress can activate TRPA1 expressed in sensory neurons.

Authors+Show Affiliations

Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom. david.andersson@kcl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18322093

Citation

Andersson, David A., et al. "Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 10, 2008, pp. 2485-94.
Andersson DA, Gentry C, Moss S, et al. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008;28(10):2485-94.
Andersson, D. A., Gentry, C., Moss, S., & Bevan, S. (2008). Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(10), 2485-94. https://doi.org/10.1523/JNEUROSCI.5369-07.2008
Andersson DA, et al. Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress. J Neurosci. 2008 Mar 5;28(10):2485-94. PubMed PMID: 18322093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. AU - Andersson,David A, AU - Gentry,Clive, AU - Moss,Sian, AU - Bevan,Stuart, PY - 2008/3/7/pubmed PY - 2008/4/9/medline PY - 2008/3/7/entrez SP - 2485 EP - 94 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 28 IS - 10 N2 - Transient receptor potential A1 (TRPA1) is expressed in a subset of nociceptive sensory neurons where it acts as a sensor for environmental irritants, including acrolein, and some pungent plant ingredients such as allyl isothiocyanate and cinnamaldehyde. These exogenous compounds activate TRPA1 by covalent modification of cysteine residues. We have used electrophysiological methods and measurements of intracellular calcium concentration ([Ca(2+)](i)) to show that TRPA1 is activated by several classes of endogenous thiol-reactive molecules. TRPA1 was activated by hydrogen peroxide (H(2)O(2); EC(50), 230 microM), by endogenously occurring alkenyl aldehydes (EC(50): 4-hydroxynonenal 19.9 microM, 4-oxo-nonenal 1.9 microM, 4-hydroxyhexenal 38.9 microM) and by the cyclopentenone prostaglandin, 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ(2), EC(50): 5.6 microM). The effect of H(2)O(2) was reversed by treatment with dithiothreitol indicating that H(2)O(2) acts by promoting the formation of disulfide bonds whereas the actions of the alkenyl aldehydes and 15d-PGJ(2) were not reversed, suggesting that these agents form Michael adducts. H(2)O(2) and the naturally occurring alkenyl aldehydes and 15d-PGJ(2) acted on a subset of isolated rat and mouse sensory neurons [approximately 25% of rat dorsal root ganglion (DRG) and approximately 50% of nodose ganglion neurons] to evoke a depolarizing inward current and an increase in [Ca(2+)](i) in TRPA1 expressing neurons. The abilities of H(2)O(2), alkenyl aldehydes and 15d-PGJ(2) to raise [Ca(2+)](i) in mouse DRG neurons were greatly reduced in neurons from trpa1(-/-) mice. Furthermore, intraplantar injection of either H(2)O(2) or 15d-PGJ2 evoked a nocifensive/pain response in wild-type mice, but not in trpa1(-/-) mice. These data demonstrate that multiple agents produced during episodes of oxidative stress can activate TRPA1 expressed in sensory neurons. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18322093/Transient_receptor_potential_A1_is_a_sensory_receptor_for_multiple_products_of_oxidative_stress_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=18322093 DB - PRIME DP - Unbound Medicine ER -