Association of the novel non-AT(1), Non-AT(2) angiotensin binding site with neuronal cell death

Rashid, Mamoon, Arumugam, Thiruma V. and Karamyan, Vardan T. (2010) Association of the novel non-AT(1), Non-AT(2) angiotensin binding site with neuronal cell death. Journal of Pharmacology And Experimental Therapeutics, 335 3: 754-761. doi:10.1124/jpet.110.171439


Author Rashid, Mamoon
Arumugam, Thiruma V.
Karamyan, Vardan T.
Title Association of the novel non-AT(1), Non-AT(2) angiotensin binding site with neuronal cell death
Journal name Journal of Pharmacology And Experimental Therapeutics   Check publisher's open access policy
ISSN 0022-3565
1521-0103
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1124/jpet.110.171439
Volume 335
Issue 3
Start page 754
End page 761
Total pages 8
Place of publication Bethesda, MD U.S.A.
Publisher American Society for Pharmacology and Experimental Therapeutics
Collection year 2011
Language eng
Formatted abstract
We have discovered a non-AT1, non-AT2 angiotensin binding site in rodent and human brain membranes, which, based on its pharmacological/biochemical properties and tissue distribution, is different from angiotensin receptors and key proteases processing angiotensins. In this study, the novel angiotensin binding site was localized to a specific brain cell type by using radioligand receptor binding assays. Our results indicate that the novel binding site is expressed in mouse primary cortical neuronal membranes but not in primary cortical astroglial and bEnd.3 brain capillary endothelial cell membranes. Whole-cell binding assays in neurons showed that the binding site faces the outer side of the plasma membrane. Consistent with our previous observations, the novel binding site was unmasked by the sulfhydryl reagent p-chloromercuribenzoate. This effect had a bell-shaped curve and was reversed by reduced glutathione, indicating that the function of the binding site might be regulated by the redox state of the environment. Density of the novel binding site measured by saturation binding assays was significantly increased in neuronal membranes of cells challenged in four in vitro models of cell death (oxygen-glucose deprivation, sodium azide-induced hypoxia, N-methyl-D-aspartate neurotoxicity, and hydrogen peroxide neurotoxicity). In addition, our in vivo data from developing mouse brains showed that the density of the novel angiotensin binding site changes similarly to the pattern of neuronal death in maturating brain. This is the first time that evidence is provided on the association of the novel angiotensin binding site with neuronal death, and future studies directed toward understanding of the functions of this protein are warranted.
Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.
Keyword Brain Renin-angiotensin
Smooth-muscle-cells
Rat-brain
Fluorescence Detection
Radioligand binding
Nadph oxidase
Receptors
Culture
Phosphorylation
Microdialysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online before print September 22, 2010,

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
 
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Created: Sun, 12 Dec 2010, 00:04:56 EST