| RNA--induced silencing of the plasma membrane Ca2+-ATPase 2 in neuronal cells: effects on Ca2+ homeostasis and cell viability. | |
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MedLine Citation:
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PMID: 17488275 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Intraneuronal calcium ([Ca(2+)](i)) regulation is altered in aging brain, possibly because of the changes in critical Ca(2+) transporters. We previously reported that the levels of the plasma membrane Ca(2+)-ATPase (PMCA) and the V(max) for enzyme activity are significantly reduced in synaptic membranes in aging rat brain. The goal of these studies was to use RNA(i) techniques to suppress expression of a major neuronal isoform, PMCA2, in neurons in culture to determine the potential functional consequences of a decrease in PMCA activity. Embryonic rat brain neurons and SH-SY5Y neuroblastoma cells were transfected with in vitro--transcribed short interfering RNA or a short hairpin RNA expressing vector, respectively, leading to 80% suppression of PMCA2 expression within 48 h. Fluorescence ratio imaging of free [Ca(2+)](i) revealed that primary neurons with reduced PMCA2 expression had higher basal [Ca(2+)](i), slower recovery from KCl-induced Ca(2+) transients, and incomplete return to pre-stimulation Ca(2+) levels. Primary neurons and SH-SY5Y cells with PMCA2 suppression both exhibited significantly greater vulnerability to the toxicity of various stresses. Our results indicate that a loss of PMCA such as occurs in aging brain likely leads to subtle disruptions in normal Ca(2+) signaling and enhanced susceptibility to stresses that can alter the regulation of Ca(2+) homeostasis. |
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Authors:
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Denzyl Fernandes; Asma Zaidi; Jennifer Bean; Dongwei Hui; Mary L Michaelis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-05-04 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 102 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-06-28 Completed Date: 2007-09-07 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 454-65 Citation Subset: IM |
Affiliation:
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Gene Logic, Inc., Cambridge, Massachusetts, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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genetics,
metabolism Animals Calcium / metabolism Calcium Signaling / genetics* Cell Line, Tumor Cell Membrane / enzymology*, genetics Cell Survival / genetics Cells, Cultured Down-Regulation / genetics* Gene Expression Regulation, Enzymologic / genetics Homeostasis / genetics Humans Neurons / enzymology* Plasma Membrane Calcium-Transporting ATPases / genetics, metabolism* RNA Interference / physiology* RNA, Small Interfering / genetics Rats Rats, Sprague-Dawley |
| Grant Support | |
ID/Acronym/Agency:
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P01AG12993/AG/NIA NIH HHS; P20RR017708/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 7440-70-2/Calcium; EC 3.6.3.8/Plasma Membrane Calcium-Transporting ATPases |
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