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1.
Neuron ; 86(3): 665-71, 2015 May 06.
Article in English | MEDLINE | ID: mdl-25950634

ABSTRACT

Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons. This action required the two TRPs Nanchung (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and Iav together sufficed to confer cellular insecticide responses in vivo and in vitro, and the two insecticides were identified as specific agonists of Nan-Iav complexes that, by promoting cellular calcium influx, silence the stretch receptor cells. This establishes TRPs as insecticide targets and defines specific agonists of insect TRPs. It also shows that TRPs can render insecticides cell-type selective and puts forward TRP targets to reduce side effects on non-target species.


Subject(s)
Drosophila Proteins/drug effects , Ion Channels/drug effects , Mechanoreceptors/drug effects , Pesticides/pharmacology , Quinazolinones/pharmacology , Transient Receptor Potential Channels/drug effects , Triazines/pharmacology , Acoustic Stimulation , Action Potentials/drug effects , Action Potentials/genetics , Animals , Animals, Genetically Modified , Arthropod Antennae/cytology , CHO Cells , Cricetulus , Drosophila , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Gravity Sensing/drug effects , Gravity Sensing/genetics , Ion Channels/genetics , Ion Channels/metabolism , Larva , Mechanoreceptors/physiology , Movement/drug effects , Neurons/drug effects , Transcription Factors/genetics , Transcription Factors/metabolism , Transient Receptor Potential Channels/genetics
2.
Am J Clin Nutr ; 79(6): 1053-9, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15159236

ABSTRACT

BACKGROUND: Identification of allelic variants in a single gene that determine the phytate content of maize kernels and the subsequent breeding of low-phytate maize have facilitated studies designed to determine quantitatively the effects of maize phytate on the bioavailability of minerals in maize. OBJECTIVE: The objective was to determine the relation between the fractional absorption of zinc (FAZ) and the phytate content and phytate:zinc molar ratios of maize tortillas prepared from hybrids with different phytate contents. DESIGN: Six healthy adults were fed, as the only food for 2 d, maize tortillas prepared from 1 of 2 low-phytate mutants: lpa1-1 (lpa1-1-LP) or Nutridense Low Phytate (ND-LP), which have phytate reductions of approximately 60% and approximately 80%, respectively, compared with their respective wild-type isohybrids. Four additional subjects were fed tortillas prepared from the corresponding wild-type isohybrids (lpa1-1-WT and ND-WT) according to the same study design. Meals were extrinsically labeled with zinc stable isotopes, and FAZ was determined with a dual-isotope-tracer ratio technique. Overall FAZ values were examined in relation to dietary phytate and phytate:zinc molar ratios by using a mixed nonlinear regression model. RESULTS: The mean (+/-SD) FAZ values from tortillas prepared from ND-LP, lpa1-1-LP, lpa1-1-WT, and ND-WT were 0.38 +/- 0.07, 0.28 +/- 0.04, 0.15 +/- 0.07, and 0.13 +/- 0.05, respectively. A negative relation (P < 0.001) was found between FAZ and both dietary phytate and the phytate:zinc molar ratio. The effect of dietary zinc (8-14 mg Zn/d) under these experimental conditions was not significant. CONCLUSIONS: FAZ from maize tortillas is positively related to the extent of phytate reduction achieved with low-phytate hybrids.


Subject(s)
Diet , Phytic Acid/pharmacology , Zea mays/genetics , Zinc/pharmacokinetics , Adult , Biological Availability , Female , Humans , Intestinal Absorption , Male , Phytic Acid/administration & dosage , Zinc/administration & dosage , Zinc Isotopes/pharmacokinetics
3.
Phytochemistry ; 62(5): 691-706, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12620321

ABSTRACT

myo-Inositol-1,2,3,4,5,6-hexakisphosphate (Ins P(6) or "phytic acid") typically represents approximately 75% of the total phosphorus and >80% of soluble myo-inositol (Ins) phosphates in seeds. The seed phosphorus and Ins phosphate phenotypes of four non-lethal barley (Hordeum vulgare L.) low phytic acid mutations are described. In seeds homozygous for M 635 and M 955 reductions in Ins P(6), approximately 75 and >90% respectively, are accompanied by reductions in other Ins phosphates and molar-equivalent increases in Pi. This phenotype suggests a block in supply of substrate Ins. In seeds homozygous for barley low phytic acid 1-1 (lpa1-1), a 45% decrease in Ins P(6) is mostly matched by an increase in Pi but also accompanied by small increases in Ins(1,2,3,4,6)P(5). In seeds homozygous for barley lpa2-1, reductions in seed Ins P(6) are accompanied by increases in both Pi and in several Ins phosphates, a phenotype that suggests a lesion in Ins phosphate metabolism, rather than Ins supply. The increased Ins phosphates in barley lpa2-1 seed are: Ins(1,2,3,4,6)P(5); Ins(1,2,4,6)P(4) and/or its enantiomer Ins(2,3,4,6)P(4); Ins(1,2,3,4)P(4) and/or its enantiomer Ins(1,2,3,6)P(4); Ins(1,2,6)P(3) and/or its enantiomer Ins(2,3,4)P(3); Ins(1,5,6)P(3) and/or its enantiomer Ins(3,4,5)P(3) (the methods used here cannot distinguish between enantiomers). This primarily "5-OH" series of Ins phosphates differs from the "1-/3-OH" series observed at elevated levels in seed of the maize lpa2 genotype, but previous chromosomal mapping data indicated that the maize and barley lpa2 loci might be orthologs of a single ancestral gene. Therefore one hypothesis that might explain the differing lpa2 phenotypes is that their common ancestral gene encodes a multi-functional, Ins phosphate kinase with both "1-/-3-" and "5-kinase" activities. A putative pyrophosphate-containing Ins phosphate, possibly an Ins P(7), was also observed in the mature seed of all barley genotypes except lpa2-1. Barley M 955 indicates that at least for this species, the ability to accumulate Ins P(6) can be nearly abolished while retaining at least short-term ( approximately 1.0 years) viability.


Subject(s)
Hordeum/genetics , Inositol Phosphates/metabolism , Phosphorus/analysis , Phytic Acid/biosynthesis , Seeds/genetics , Seeds/metabolism , Chromatography, High Pressure Liquid , Genotype , Hordeum/chemistry , Hordeum/metabolism , Inositol Phosphates/chemistry , Inositol Phosphates/genetics , Mutation , Nuclear Magnetic Resonance, Biomolecular , Phenotype , Seeds/chemistry , Seeds/growth & development , Stereoisomerism , Zea mays/chemistry , Zea mays/genetics , Zea mays/metabolism
4.
Am J Clin Nutr ; 76(3): 556-9, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12197999

ABSTRACT

BACKGROUND: Phytic acid reduction in cereal grains has been accomplished with plant genetic techniques. These low-phytic acid grains provide a strategy for improving the mineral (eg, zinc) status in populations that are dependent on grains, including maize (Zea mays L.), as major dietary staples. OBJECTIVE: The objective was to compare the fractional absorption of zinc from polenta prepared from maize low in phytic acid with that prepared from a wild-type isohybrid maize (control) after short-term consumption by adults whose habitual diet is low in phytic acid. DESIGN: Healthy adults served as their own control subjects in a crossover design. All meals on 1 d consisted of polenta prepared from a low-phytic acid maize homozygous for the recessive low phytic acid 1-1 (lpa1-1). On the preceding or following day, all meals consisted of polenta prepared from a sibling isohybrid homozygous wild-type maize with a "normal" phytic acid content. The low-phytic acid maize contained approximately 60% less phytic acid than did the wild-type maize. All test meals were extrinsically labeled with zinc stable-isotope tracers. The fractional absorption of zinc was determined on the basis of fecal enrichment. RESULTS: The molar ratios of phytic acid to zinc in the polenta prepared from lpa1-1 maize and the wild-type maize were 17:1 and 36:1, respectively. The corresponding fractional absorptions of zinc were 0.30 +/- 0.13 and 0.17 +/- 0.11, respectively (P < 0.005). CONCLUSION: Substitution of a low-phytic acid grain in a maize-based diet is associated with a substantial increase in zinc absorption.


Subject(s)
Diet , Phytic Acid/analysis , Zea mays/chemistry , Zinc/pharmacokinetics , Absorption , Adult , Biological Availability , Cross-Over Studies , Feces/chemistry , Female , Genetic Engineering , Humans , Male , Zea mays/genetics , Zinc/administration & dosage , Zinc Isotopes
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