Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic is ubiquitously present in the environment; it is a known human carcinogen and paradoxically it is also a successful drug for the clinical remission of acute promyelocytic leukemia (APL). The cellular responses induced by arsenite treatment have been investigated for years; however, the precise mechanisms underlying its cytotoxicity and therapeutic activity remain unclear. Here we report the use of mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in HL-60 cells that were untreated or treated with a clinically relevant concentration of arsenite. Our results revealed that, among the 1067 proteins quantified in both forward and reverse SILAC measurements, 56 had significantly altered levels of expression induced by arsenite treatment. These included the up-regulation of core histones, neutrophil elastase, alpha-mannosidase as well as the down-regulation of fatty acid synthase and protein phosphatase 1 alpha. We further demonstrated that the arsenite-induced growth inhibition of HL-60 cells could be rescued by treatment with palmitate, the final product of fatty acid synthase, supporting that arsenite exerts its cytotoxic effect, in part, via suppressing the expression of fatty acid synthase and inhibiting the endogenous production of fatty acid. The results from the present study offered important new knowledge for gaining insights into the molecular mechanisms of action of arsenite.
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PMID:Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in HL-60 cells induced by arsenite treatment. 2005 Jun 88

Arsenic, a major environmental toxicant and pollutant, is a global public health concern. Among its many adverse effects, arsenic is immunotoxic, but its effects on human neutrophil functions are not yet well-defined. In this study, we aimed to evaluate the in vitro effects of acute low-dose NaAsO2 exposure on human polymorphonuclear neutrophils (PMNs) for 12 h on the following innate defense mechanisms: formation of neutrophil extracellular traps (NETs), production of reactive oxygen species (ROS), and phagocytosis. Phorbol myristate acetate (PMA) was added to induce NETs formation, which was quantified by measuring cell-free extracellular DNA (cf-DNA), myeloperoxidase-conjugated (MPO)-DNA and neutrophil elastase-conjugated (NE)-DNA, and confirmed by immunofluorescence labeling and imaging. Extracellular bactericidal activity by NETs was evaluated by co-culturing Escherichia coli and PMNs in the presence of a phagocytic inhibitor. Levels of NETs in the culture medium after PMA stimulation was significantly lower in PMNs pre-exposed to arsenic than those not exposed to arsenic. Immunofluorescence staining and extracellular bactericidal activity by NETs revealed similar results. Phagocytosis and ROS production by PMNs were also significantly reduced by arsenic pre-exposure. Together, our findings provide new insights in arsenic immunotoxicity and suggest how it increases susceptibility to infectious diseases in humans.
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PMID:Inorganic arsenic administration suppresses human neutrophil function in vitro. 3306 58