Abstract
We have previously demonstrated that concentrations of 1-10 microM of methylmercuric chloride (MeHgCl) that are cytotoxic to monocytes-macrophages can curiously inhibit neutrophil apoptosis by a yet unknown mechanism. In the present study, we demonstrate that, as with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), a classical inhibitor of neutrophil apoptosis, treatment of cells with 5 microM MeHgCl induces de novo protein synthesis and prevents the loss of expression of the antiapoptotic Mcl-1 protein. The expression of the cytoskeletal proteins gelsolin, paxillin and vinculin was similar in MeHgCl- or GM-CSF-induced suppression of apoptosis. However, MeHgCl prevents the degradation of vimentin differently than GM-CSF. Apoptosis was further confirmed by flow cytometry (FITC annexin-V), and by monitoring CD16 cell surface expression. Curiously, unlike GM-CSF, MeHgCl did not prevent CD16 shedding. We conclude that, like GM-CSF, MeHgCl can delay neutrophil apoptosis by inducing de novo protein synthesis and by preventing the loss of the antiapoptotic Mcl-1 protein. However, unlike GM-CSF, MeHgCl induces an atypical degradation of vimentin without preventing CD16 shedding.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Cell Membrane / drug effects
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Cell Survival / drug effects
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Cell Survival / physiology*
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / physiology
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Dose-Response Relationship, Drug
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Gelsolin / biosynthesis
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Gelsolin / genetics
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Gelsolin / physiology
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Gene Expression / drug effects
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Interleukin-5 / metabolism
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Interleukin-5 / pharmacology
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Methylmercury Compounds / metabolism
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Methylmercury Compounds / pharmacology*
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neutrophils / drug effects*
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Neutrophils / metabolism
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Paxillin
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Phosphoproteins / biosynthesis
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Phosphoproteins / genetics
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Phosphoproteins / physiology
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Proto-Oncogene Proteins c-bcl-2*
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Receptors, IgG / metabolism
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Sulfur Radioisotopes / metabolism
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Vimentin / antagonists & inhibitors
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Vimentin / biosynthesis
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Vimentin / genetics
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Vinculin / biosynthesis
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Vinculin / genetics
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Vinculin / physiology
Substances
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Cytoskeletal Proteins
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Gelsolin
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Interleukin-5
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Methylmercury Compounds
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Myeloid Cell Leukemia Sequence 1 Protein
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Neoplasm Proteins
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PXN protein, human
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Paxillin
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Phosphoproteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, IgG
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Sulfur Radioisotopes
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Vimentin
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Vinculin
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Granulocyte-Macrophage Colony-Stimulating Factor
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methylmercuric chloride