Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP.
Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): a probable mechanism of acute pulmonary toxicity for DEP.
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DOI：
10.1021/tx200123z
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发表时间：
2011-06-20
影响因子：
4.1
通讯作者：
Reilly CA
中科院分区：
文献类型：
--
作者：
Deering-Rice CE;Romero EG;Shapiro D;Hughen RW;Light AR;Yost GS;Veranth JM;Reilly CA
Inhalation of environmental particulate matter (PM) is correlated with adverse health effects in humans, but gene products that couple detection with cellular responses, and the specific properties of PM that target different pathways, have not been fully elucidated. TRPA1 and V1 are two cation channels expressed by sensory neurons and non-neuronal cells of the respiratory tract that have been implicated as possible mediators of PM toxicity. The goals of this research were to determine if environmental PM preferentially activated TRPA1 and to elucidate the criteria responsible for selectivity. Quantification of TRPA1 activation by 4 model PM revealed that diesel exhaust PM (DEP) and coal fly ash PM (CFA1) were TRPA1 agonists at concentrations >0.077 mg/ml. DEP was more potent and approximately 97% of the activity of DEP was recovered by serial extraction of the solid DEP with ethanol and hexane:n-butyl chloride. Modification of the electrophile/agonist binding sites on TRPA1 (C621, C641, C665 and K710) to non-nucleophilic residues reduced TRPA1 activation by DEP and abolished activation by DEP extracts as well as multiple individual electrophilic chemical components of DEP. However, responses to CFA1 and DEP solids were not affected by these mutations. Activity-guided fractionation of DEP and high resolution mass spectroscopy identified several new DEP-derived TRPA1 agonists and activation of mouse dorsal root ganglion neurons demonstrated TRPA1 is a primary target for DEP in a heterogeneous population of primary sensory nerves. It is concluded that TRPA1 is a specific target for electrophilic chemical components of DEP and proposed that activation of TRPA1 in the respiratory tract is likely to be an important mechanism for DEP pneumotoxicity.
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影响因子：
10.4
作者：
Li J;Kanju P;Patterson M;Chew WL;Cho SH;Gilmour I;Oliver T;Yasuda R;Ghio A;Simon SA;Liedtke W
通讯作者：
Liedtke W
影响因子：
2.5
作者：
Anand, U.;Otto, W. R.;Anand, P.
通讯作者：
Anand, P.
影响因子：
15.9
作者：
Bessac, Bret F.;Sivula, Michael;Jordt, Sven-Eric
通讯作者：
Jordt, Sven-Eric
DOI：
10.1152/physiol.00026.2008
发表时间：
2008-12
期刊：
Physiology (Bethesda, Md.)
影响因子：
--
作者：
Bessac BF;Jordt SE
通讯作者：
Jordt SE
影响因子：
3.8
作者：
Agopyan, N;Bhatti, T;Simon, SA
通讯作者：
Simon, SA