The Keap1-Nrf2 system is the major regulatory pathway of cytoprotective gene expression against oxidative and/or electrophilic stresses. Keap1 acts as a stress sensor protein in this system. While Keap1 constitutively suppresses Nrf2 activity under unstressed conditions, oxidants or electrophiles provoke the repression of Keap1 activity, inducing the Nrf2 activation. However, the precise molecular mechanisms behind the liberation of Nrf2 from Keap1 repression in the presence of stress remain to be elucidated. We hypothesized that oxidative and electrophilic stresses induce the nuclear accumulation of Nrf2 by affecting the Keap1-mediated rapid turnover of Nrf2, since such accumulation was diminished by the protein synthesis inhibitor cycloheximide. While both the Cys273 and Cys288 residues of Keap1 are required for suppressing Nrf2 nuclear accumulation, treatment of cells with electrophiles or mutation of these cysteine residues to alanine did not affect the association of Keap1 with Nrf2 either in vivo or in vitro. Rather, these treatments impaired the Keap1-mediated proteasomal degradation of Nrf2. These results support the contention that Nrf2 protein synthesized de novo after exposure to stress accumulates in the nucleus by bypassing the Keap1 gate and that the sensory mechanism of oxidative and electrophilic stresses is closely linked to the degradation mechanism of Nrf2.

Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1.

Chlorpyrifos is a member of the organophosphorus or organophosphate class of insecticides. This class has become one of the most widely used groups of pest control chemicals. In 1989 nearly 40% of the $6.2 billion global insecticide market was comprised of organophosphates (OPs) (Phillips and McDougall 1990). Although Clermont (1854) had first synthesized tetraethylpyrophosphate (TEPP), it was not until much later that the insecticidal properties of this OP were described (Schrader 1942). This milestone led to further synthetic work with insecticidal OPs and thus provided the impetus that would lead to the launch of an entirely new class of insecticides. Early OPs found to be efficacious for insect control and thus brought into widespread use included parathion (1944) and malathion (1952) (Matsumura 1985). These successes stimulated further discovery work on the part of synthetic chemists and entomologists within a number of research organizations.

Environmental Fate of Chlorpyrifos

Three mathematical models were proposed to describe the effects of sorption of both bacteria and the herbicide (2,4-dichlorophenoxy)acetic acid (2,4-D) on the biological degradation rates of 2,4-D in soils. Model 1 assumed that sorbed 2,4-D is not degraded, that only bacteria in solution are capable of degrading 2,4-D in solution, and that sorbed bacteria are not capable of degrading either sorbed or solution 2,4-D. Model 2 stated that only bacteria in the solution phase degrade 2,4-D in solution and that only sorbed bacteria degrade sorbed 2,4-D. Model 3 proposed that sorbed 2,4-D is completely protected from degradation and that both sorbed and solution bacteria are capable of degrading 2,4-D in solution. These models were tested by a series of controlled laboratory experiments. Models 1 and 2 did not describe the data satisfactorily and were rejected. Model 3 described the experimental results quite well, indicating that sorbed 2,4-D was completely protected from biological degradation and that sorbed- and solution-phase bacteria degraded solution-phase 2,4-D with almost equal efficiencies.

https://aem.asm.org/content/aem/49/3/582.full.pdf

Effects of sorption on biological degradation rates of (2,4-dichlorophenoxy) acetic acid in soils.

A Naturally Occurring Point Mutation Confers Broad Range Tolerance to Herbicides That Target Acetolactate Synthase

Sunlight photodegradation is one of the most destructive pathways for pesticides after their release into the environment. Plant surfaces, especially leaf surfaces, are the first reaction environment for a pesticide molecule after application, and spray drift would indirectly present a similar situation. Photolysis on soil surfaces becomes important when a pesticide is directly applied to soil or not significantly intercepted by plants, providing that the leaf cover does not shade the ground from sunlight. Because the foliar interception of pesticides depends on plant species and usually increases with their growth stage (Linders et al. 2000), the importance of soil photolysis is considered to be lessened when plants become mature. Spray drift after pesticide application or washoff from plants by rain is the indirect route by which a pesticide reaches the soil.

https://bilder.buecher.de/zusatz/14/14812/14812358_lese_1.pdf?origin=publication_detail

Photodegradation of Pesticides on Plant and Soil Surfaces

Two new structural classes of herbicide have been discovered which are based on the 1,2,4-triazolo[1,5-a]pyrimidine ring system. These compounds are related to the known herbicidal sulfonylureas and imidazolinones and other studies have shown that they have a similar mode of action, involving the inhibition of branched-chain amino acid biosynthesis, the site of action being the enzyme acetolactate synthase. The design, synthesis and structure- activity relationships of these new classes of compounds are described.

New herbicidal derivatives of 1,2,4-triazolo [1,5-a] pyrimidine

History will record that eventually there was a relatively simple accommodation to the extraordinarily complex problem of defining and using principles of degradation to predict this aspect of the behavior of pesticides in soil. So it is with many scientific endeavors.

Principles of Pesticide Degradation in Soil

The hydrolysis rate of chlorpyrifos (the active ingredient of DURSBAN® and LORSBAN® insecticides, registered trademarks of The Dow Chemical Company, Midland, Michigan) in water followed simple first-order kinetics over the concentration range, 3×10−9 to 3×10−7M. In buffered distilled water at 25°C and pH 8.1, 6.9, and 4.7, the half-life was 22.8, 35.3, and 62.7 days, respectively. Additional data were obtained for rates at 15° and 35°C. The activation energy for the reaction under these conditions was 21.2 kcal/mole. A 16-fold rate enhancement was demonstrated in canal and pond water at 25°C. Likewise, there was a catalytic effect on the hydrolysis rate in the presence of copper (II) ion.

The hydrolysis rate of chlorpyrifos,O-O-diethylO-(3,5,6-trichloro-2-pyridyl) phosphorothioate, and its dimethyl analog, chlorpyrifos-methyl, in dilute aqueous solution

Richard W. Meikle

Papers

New herbicidal derivatives of 1,2,4-triazolo [1,5-a] pyrimidine

Principles of Pesticide Degradation in Soil

The hydrolysis rate of chlorpyrifos,O-O-diethylO-(3,5,6-trichloro-2-pyridyl) phosphorothioate, and its dimethyl analog, chlorpyrifos-methyl, in dilute aqueous solution

Metabolism of Tordon Herbicide (4-Amino-3,5,6-trichloropicolinic Acid) in Cotton and Decomposition in Soil

Measurement and Prediction of Picloram Disappearance Rates from Soil