Document Detail


Intracellular zinc elevation measured with a "calcium-specific" indicator during ischemia and reperfusion in rat hippocampus: a question on calcium overload.
MedLine Citation:
PMID:  17035527     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Much of our current evidence concerning of the role of calcium (Ca2+) as a second messenger comes from its interaction with fluorescent probes; however, many Ca2+ probes also have a higher affinity for another divalent cation: zinc (Zn2+). In this study, using a selective Zn2+ probe (Newport Green), we investigated the accumulation of intracellular Zn2+ transients in acute rat hippocampal slices during ischemia, simulated by oxygen and glucose deprivation (OGD). Subsequent reperfusion with glucose-containing oxygenated medium resulted in an additional increase in intracellular Zn2+. Such observations compelled us to investigate the contribution of Zn2+ to the alleged intracellular Ca2+ overload occurring in ischemia and reperfusion. Using confocal fluorescent microscopy of Calcium Green-1, a widely used Ca2+ indicator, we detected increases in fluorescence intensity during OGD and reperfusion. However, application of a Zn2+ chelator, at the peak of the fluorescence elevation (interpreted as Ca2+ overload), resulted in a significant drop in intensity, suggesting that rising Zn2+ is the primary source of the increasing Calcium Green-1 fluorescence. Finally, staining with the cell viability indicator propidium iodide revealed that Zn2+ is responsible for the ischemic neuronal cell death, because Zn2+ chelation prevented cells from sustaining ischemic damage. Current cellular models of ischemic injury center on Ca2+-mediated excitotoxicity. Our results indicate that Zn2+ elevation contributes to conventionally recognized Ca2+ overload and also suggest that the role of Ca2+ in neurotoxicity described previously using Ca2+ probes may need to be re-examined to determine whether effect previously attributed to Ca2+ could, in part, be attributable to Zn2+.
Authors:
Christian J Stork; Yang V Li
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  26     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-12     Completed Date:  2006-11-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10430-7     Citation Subset:  IM    
Affiliation:
Department of Biomedical Science, Program in Molecular and Cellular Biology, Ohio University, Athens, Ohio 45701, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / analysis,  metabolism*
Cell Death / physiology
Cell Hypoxia / physiology
Hippocampus / chemistry,  metabolism*
Intracellular Fluid / chemistry,  metabolism*
Male
Rats
Rats, Sprague-Dawley
Reperfusion / methods
Zinc / analysis,  metabolism*
Chemical
Reg. No./Substance:
7440-66-6/Zinc; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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