Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gamma-isomer of hexachlorocyclohexane (gamma-HCCH), which displays structural homology with inositol, was found to induce an initial influx of Ca2+ in mouse peritoneal macrophages. This was responsible for Ca(2+)-induced Ca2+ release via inositol 1,4,5-trisphosphate produced by phospholipase C and resulted in a sustained increase of cytoplasmic free Ca2+ concentration ([Ca2+]i). Entry of Ca2+ evoked by gamma-HCCH also stimulated phospholipase D, as well as the generation of reactive oxygen species formed by NADPH oxidase. These data suggest that some isoform(s) of phospholipase C, and possibly phospholipase D, can be activated by strictly Ca(2+)-dependent mechanisms. They also describe a new experimental tool allowing to trigger a selective influx of Ca2+. gamma-HCCH could thus be used in further studies aimed to delineate the role of Ca2+ entry in the subsequent activation of other signalling pathways.
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PMID:Ca(2+)-dependent activation of phospholipases C and D from mouse peritoneal macrophages by a selective trigger of Ca2+ influx, gamma-hexachlorocyclohexane. 751 Sep 60

Hexachlorocyclohexane (HCH) is a highly recalcitrant organochlorine insecticide known for its chronic toxicity. In spite of many isolated studies a clear mechanism of cytotoxic action of HCH and the structure-toxicity relationship of its isomers is not well understood. We have investigated the toxicity of HCH isomers and its mechanism in Ehrlich Ascites tumor (EAT) cells. Our studies show differential cytotoxicity of HCH isomers (alpha, beta, gamma, and delta), delta isomer being most toxic and beta the least. HCH-induced cell death was associated with induction of reactive oxygen species (ROS) formation, lipid peroxidation (LPO), and depletion of glutathione (GSH). The increase in oxidative stress was linked with increased NAD(P)H oxidase activity. HCH inhibited Na(+),K(+)-ATPase, which could be involved in raising the intracellular calcium and increased Ca(2+),Mg(2+)-ATPase activity. HCH lead to apoptotic as well as necrotic cell death as it was marked by increased caspase-3 activity and lactate dehydrogenase (LDH) leakage, respectively. Based on the results it is concluded that the HCH isomers inflict differential cytotoxicity which was highest by delta and lowest by beta. Further, this study demonstrates for the first time a clear link between Na(+),K(+)-ATPase, i[Ca(2+)] level, and oxidative stress in HCH-induced cytotoxicity.
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PMID:Stereospecificity in the cytotoxic action of hexachlorocyclohexane isomers. 1981 41