Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.1 (Mg2+-ATPase)
 1,484 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlordecone was reported to produce neurotoxicity by modulating the Na+ pump in adult rat brain. The present in vitro and in vivo studies were initiated to investigate its effect on maturing rat brain ATPases. Neonates were exposed to chlordecone for 20 d indirectly through lactation by treating the mothers po and from 21 to 50 d as adults. Brain P2 fractions were prepared from treated and control rats. Na+,K+, oligomycin-sensitive (O.S.) and oligomycin-insensitive (O.I.) Mg2+-ATPase activities were increased with age up to d 20. Na+,K+- and O.S. Mg2+-ATPases were inhibited in both in vitro and in vivo treatment with chlordecone. Both these enzymes were more sensitive to chlordecone in the neonatal brains as compared to adult rats (20-50 d). The activity of Mg2+-ATPase but not of Na+,K+-ATPase was restored to normal activity after 20 d of withdrawal of chlordecone treatment. O.I. Mg2+-ATPase was insensitive to chlordecone treatment in all age groups. Ca2+-ATPase activity was not increased with age; however, it was more sensitive to chlordecone in neonates as compared to adults. These results suggest that the Na+ pump, Ca2+-ATPase, and ATP synthesizing enzymes are highly sensitive to chlordecone during early postnatal development.
 ...
PMID:Age-related changes in rat brain ATPases during treatment with chlordecone. 247 39

Chlordecone (Kepone) is a close structural analog of mirex, but it differs considerably from mirex in toxic action. Chlordecone primarily produces neurotoxic symptoms such as tremors in humans and animals. As with other organochlorine pesticides, the mechanism of the toxic action of chlordecone is not completely understood. An attempt is made in this paper to review the effects of chlordecone on the membrane-bound adenosinetriphosphatases (ATPases) and related phenomena. Chlordecone is shown to be a potent inhibitor of ATPases in different tissue preparations of several species. The order of sensitivity of the ATPases tested to chlordecone was: oligomycin-sensitive (mitochondrial) Mg2+-ATPase greater than Na+,K+-ATPase greater than Ca2+-ATPase greater than oligomycin-insensitive Mg2+-ATPase. Compared to other tissues tested, brain Na+K+-ATPase and heart mitochondrial Mg2+-ATPase were more sensitive to chlordecone. Oligomycin-insensitive Mg2+-ATPase was the least affected enzyme. Membrane-bound Na+, K+-ATPase has been associated with catecholamine uptake processes, and inhibitors of this enzyme, such as ouabain, have been found to decrease catecholamine uptake. Chlordecone decreased the uptake of catecholamines by rat heart membranes in a dose-dependent manner. Various cellular processes such as catecholamine uptake are dependent for energy on ATP, and most of this ATP is produced in the mitochondria through oxidative phosphorylation. Oligomycin-sensitive Mg2+-ATPase is involved in this coupling process. Chlordecone inhibition of this enzyme may result in depletion of mitochondrial ATP. This chain of events suggest that chlordecone interacts with membrane ATPases and thus may impair various energy-dependent cellular processes.
 ...
PMID:Interaction of chlordecone with biological membranes. 617 65

Chlordecone, a polycyclic chlorinated insecticide known as Kepone, inhibited the activities of (Na+-K+)ATPase and Mg2+-ATPase in rat brain synaptosomes. Altered pH and specific activity curves for both enzymes demonstrated significant inhibition by chlordecone in buffered acidic, neutral and alkaline pH ranges. Noncompetitive inhibition with respect to activation by ATP in the case of (Na+-K+)ATPase was indicated by altered Vmax values with no significant change in Km values at any pH studied, except at pH 9.5. Mg2+-ATPase was inhibited uncompetitively as evidenced by altered Vmax and Km values. The activities of both ATPase were decreased in the presence of chlordecone at higher temperatures. Activation energy (delta E) values were found to be decreased significantly in the presence of chlordecone at 37 degrees. Arrhenius plots of both ATPases preincubated with chlordecone were found to be nonlinear. In the presence of chlordecone, Vmax was decreased without significant change in Km values for (Na+-K+)ATPase at all temperatures, suggesting a noncompetitive type of inhibition. In the case of Mg2+-ATPase, similar noncompetitive type inhibition was obtained at 27 degrees but not at 32 and 37 degrees. The kinetic data in general suggest that the chlordecone inhibited (Na+-K+)ATPase noncompetitively and Mg2+-ATPase uncompetitively at all pHs and temperatures studied. The present data suggest that inhibition of (Na+-K+)ATPase and Mg2+-ATPase, the two membrane-bound enzymes in synaptosomes, by chlordecone is temperature dependent and pH independent.
 ...
PMID:Effect of chlordecone on pH and temperature dependent substrate activation kinetics of rat brain synaptosomal ATPases. 619 30