Ford KA

References (4)

Title : Neonicotinoid insecticides induce salicylate-associated plant defense responses - Ford_2010_Proc.Natl.Acad.Sci.U.S.A_107_17527
Author(s) : Ford KA , Casida JE , Chandran D , Gulevich AG , Okrent RA , Durkin KA , Sarpong R , Bunnelle EM , Wildermuth MC
Ref : Proc Natl Acad Sci U S A , 107 :17527 , 2010
Abstract : Neonicotinoid insecticides control crop pests based on their action as agonists at the insect nicotinic acetylcholine receptor, which accepts chloropyridinyl- and chlorothiazolyl-analogs almost equally well. In some cases, these compounds have also been reported to enhance plant vigor and (a)biotic stress tolerance, independent of their insecticidal function. However, this mode of action has not been defined. Using Arabidopsis thaliana, we show that the neonicotinoid compounds, imidacloprid (IMI) and clothianidin (CLO), via their 6-chloropyridinyl-3-carboxylic acid and 2-chlorothiazolyl-5-carboxylic acid metabolites, respectively, induce salicylic acid (SA)-associated plant responses. SA is a phytohormone best known for its role in plant defense against pathogens and as an inducer of systemic acquired resistance; however, it can also modulate abiotic stress responses. These neonicotinoids effect a similar global transcriptional response to that of SA, including genes involved in (a)biotic stress response. Furthermore, similar to SA, IMI and CLO induce systemic acquired resistance, resulting in reduced growth of a powdery mildew pathogen. The action of CLO induces the endogenous synthesis of SA via the SA biosynthetic enzyme ICS1, with ICS1 required for CLO-induced accumulation of SA, expression of the SA marker PR1, and fully enhanced resistance to powdery mildew. In contrast, the action of IMI does not induce endogenous synthesis of SA. Instead, IMI is further bioactivated to 6-chloro-2-hydroxypyridinyl-3-carboxylic acid, which is shown here to be a potent inducer of PR1 and inhibitor of SA-sensitive enzymes. Thus, via different mechanisms, these chloropyridinyl- and chlorothiazolyl-neonicotinoids induce SA responses associated with enhanced stress tolerance.
ESTHER : Ford_2010_Proc.Natl.Acad.Sci.U.S.A_107_17527
PubMedSearch : Ford_2010_Proc.Natl.Acad.Sci.U.S.A_107_17527
PubMedID: 20876120

Title : Enzymes and inhibitors in neonicotinoid insecticide metabolism - Shi_2009_J.Agric.Food.Chem_57_4861
Author(s) : Shi X , Dick RA , Ford KA , Casida JE
Ref : Journal of Agricultural and Food Chemistry , 57 :4861 , 2009
Abstract : Neonicotinoid insecticide metabolism involves considerable substrate specificity and regioselectivity of the relevant CYP450, aldehyde oxidase, and phase II enzymes. Human CYP450 recombinant enzymes carry out the following conversions: CYP3A4, 2C19, and 2B6 for thiamethoxam (TMX) to clothianidin (CLO); 3A4, 2C19, and 2A6 for CLO to desmethyl-CLO; 2C19 for TMX to desmethyl-TMX. Human liver aldehyde oxidase reduces the nitro substituent of CLO to nitroso much more rapidly than it does that of TMX. Imidacloprid (IMI), CLO, and several of their metabolites do not give detectable N-glucuronides but 5-hydroxy-IMI, 4,5-diol-IMI, and 4-hydroxythiacloprid are converted to O-glucuronides in vitro with mouse liver microsomes and UDP-glucuronic acid or in vivo in mice. Mouse liver cytosol with S-adenosylmethionine converts desmethyl-CLO to CLO but not desmethyl-TMX to TMX. Two organophosphorus CYP450 inhibitors partially block IMI, thiacloprid, and CLO metabolism in vivo in mice, elevating brain and liver levels of the parent compounds while reducing amounts of the hydroxylated metabolites.
ESTHER : Shi_2009_J.Agric.Food.Chem_57_4861
PubMedSearch : Shi_2009_J.Agric.Food.Chem_57_4861
PubMedID: 19391582

Title : Comparative metabolism and pharmacokinetics of seven neonicotinoid insecticides in spinach - Ford_2008_J.Agric.Food.Chem_56_10168
Author(s) : Ford KA , Casida JE
Ref : Journal of Agricultural and Food Chemistry , 56 :10168 , 2008
Abstract : The metabolism of seven commercial neonicotinoid insecticides was compared in spinach seedlings (Spinacia oleracea) using HPLC-DAD and LC-MSD to analyze the large number and great variety of metabolites. The parent neonicotinoid levels in the foliage following hydroponic treatment varied from differences in uptake and persistence. The metabolic reactions included nitro reduction, cyano hydrolysis, demethylation, sulfoxidation, imidazolidine and thiazolidine hydroxylation and olefin formation, oxadiazine hydroxylation and ring opening, and chloropyridinyl dechlorination. The identified phase I plant metabolites were generally the same as those in mammals, but the phase II metabolites differed in the conjugating moieties. Novel plant metabolites were various neonicotinoid-derived O- and N-glucosides and -gentiobiosides and nine amino acid conjugates of chloropyridinylcarboxylic acid. Metabolites known to be active on nicotinic acetylcholine receptors included the desnitro- and descyanoguanidines and olefin derivatives. The findings highlight both metabolites common to several neonicotinoids and those that are compound specific.
ESTHER : Ford_2008_J.Agric.Food.Chem_56_10168
PubMedSearch : Ford_2008_J.Agric.Food.Chem_56_10168
PubMedID: 18922014

Title : Chloropyridinyl neonicotinoid insecticides: diverse molecular substituents contribute to facile metabolism in mice -
Author(s) : Ford KA , Casida JE
Ref : Chemical Research in Toxicology , 19 :944 , 2006
PubMedID: 16841963