| LPS-induced decrease in intracellular labile zinc, [Zn]i, contributes to apoptosis in cultured sheep pulmonary artery endothelial cells. | |
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MedLine Citation:
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PMID: 21239534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A role in signal transduction for a vanishingly small labile pool of intracellular zinc ([Zn](i)) has been inferred by the sensitivity of various physiological pathways to zinc chelators such as N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and/or associations with changes in nonprotein-bound zinc-sensitive fluorophores. Although we (44) reported that LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC) was exacerbated by TPEN, 1) we did not detect acute (30 min) changes in [Zn](i), and 2) it is unclear from other reports whether LPS increases or decreases [Zn](i) and whether elevations or decreases in [Zn](i) are associated with cell death and/or apoptosis. In the present study, we used both chemical (FluoZin-3 via live cell epifluorescence microscopy and fluorescence-activated cell sorting) and genetic (luciferase activity of a chimeric reporter encoding zinc-sensitive metal-response element and changes in steady-state mRNA of zinc importer, SLC39A14 or ZIP14) techniques to show that LPS caused a delayed time-dependent (2-4 h) decrease in [Zn](i) in SPAEC. A contributory role of decreases in [Zn](i) in LPS-induced apoptosis (as determined by caspase-3/7 activation, annexin-V binding, and cytochrome c release) in SPAECs was revealed by mimicking the effect of LPS with the zinc chelator, TPEN, and inhibiting LPS- (or TPEN)-induced apoptosis with exogenous zinc. Collectively, these are the first data demonstrating a signaling role for decrease in [Zn](i) in pulmonary endothelial cells and suggest that endogenous levels of labile zinc may affect sensitivity of pulmonary endothelium to the important and complex proapoptotic stimulus of LPS. |
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Authors:
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Kalidasan Thambiayya; Karla J Wasserloos; Zhentai Huang; Valerian E Kagan; Claudette M St Croix; Bruce R Pitt |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-01-14 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: 300 ISSN: 1522-1504 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-31 Completed Date: 2011-09-15 Revised Date: 2012-04-02 |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
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Languages: eng Pagination: L624-32 Citation Subset: IM |
Affiliation:
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Department of Bioengineering, University of Pittsburgh and Universityof Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Caspase 3 / metabolism Caspase 7 / metabolism Cation Transport Proteins / genetics, metabolism Cell Survival / drug effects Cells, Cultured Endothelial Cells / cytology*, drug effects, enzymology, metabolism* Enzyme Activation / drug effects Flow Cytometry Genes, Reporter Intracellular Space / drug effects, metabolism* Lipopolysaccharides / pharmacology* Mitochondria / drug effects, metabolism Pulmonary Artery / cytology* RNA, Messenger / genetics, metabolism Sheep Signal Transduction / drug effects Spectrometry, Fluorescence Up-Regulation / drug effects Zinc / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL 70755/HL/NHLBI NIH HHS; R01 HL081421/HL/NHLBI NIH HHS; R37 HL65697/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cation Transport Proteins; 0/Lipopolysaccharides; 0/RNA, Messenger; 7440-66-6/Zinc; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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