TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD

Stokes, Alexander J.; Wakano, Clay; Koblan‐Huberson, Murielle; Adra, Chaker N.; Fleig, Andrea; Turner, Helen

doi:10.1016/j.cellsig.2005.12.009

Cited by 97 publications

(89 citation statements)

References 52 publications

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“…NaOCl induced sizable currents in hTRPA1-transfected HEK293t cells that desensitized in the continuous presence of the agonist ( Figure 2, C and D). Currents and their kinetic properties were very similar to those of previously reported hTRPA1 currents recorded with other agonists in the presence of Ca 2+ (50,51). TRPA1-mediated Ca 2+ influx was also activated by chloramine-T (N-chloro-sodium-p-toluenesulphenamide), a chlorine-releasing chemical widely used as a disinfectant (EC 50 , 11 ± 1 μM; Figure 2, E and F).…”

Section: Figuresupporting

confidence: 63%

TRPA1 is a major oxidant sensor in murine airway sensory neurons

Bessac¹,

Sivula²,

Hehn³

et al. 2008

J. Clin. Invest.

401

394

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Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca 2+ influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1 -/-mice displayed profound deficiencies in hypochlorite-and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo.

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Section: Figuresupporting

confidence: 63%

TRPA1 is a major oxidant sensor in murine airway sensory neurons

Bessac¹,

Sivula²,

Hehn³

et al. 2008

J. Clin. Invest.

401

394

View full text Add to dashboard Cite

show abstract

“…Just recently, Stokes et al found TRPA1 protein by immunostaining in human intestinal mucosa [11] yet no physiological function of TRPA1 in small intestine has been described to date.…”

Section: Discussionmentioning

confidence: 99%

TRPA1 channel activation induces cholecystokinin release via extracellular calcium

et al. 2007

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TRPA1 channels are non-selective cation channels activated by plant derived pungent products including allyl isothiocyanate (AITC) from mustard. Therefore, possible intestinal secretory functions of these channels were investigated. We detected TRPA1 mRNA in mouse and human duodenal mucosa and in intestinal mouse neuroendocrine STC-1 cells. Stimulation of STC-1 cells with AITC increased intracellular calcium ([Ca 2+ ] i ) and significantly stimulated cholecystokinin secretion by 6.7-fold. AITC induced cholecystokinin release was completely blocked by TRPA1 antagonist ruthenium red and depletion of extracellular calcium and reduced by 36% by nimodipine and nifedipine. This suggests that spices in our daily food might stimulate digestive functions.

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“…17 Although TRPA1 has been characterized and studied mainly in the nervous system, its expression was also reported in non-neuronal tissues such as skeletal muscle, lung, small intestine, colon and pancreas. 18 TRPA1 is activated by a wide spectrum of chemical and mechanical stimuli; TRPA1 is known to respond to dietary irritants such as isothyocyanates (mustard oil, wasabi, horseradish) and allycin (garlic), to name only a few. [19][20][21][22] Several endogenous pro-inflammatory mediators, including cyclopentane prostaglandins and byproducts of oxidative stress (4-hydroxynonenal [4-HNE], 4-oxononenal), have been shown to directly activate TRPA1 by covalent modification of cysteine residues on the channel.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%