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Differential Effect of Nimodipine in Attenuating Iron-Induced Toxicity in Brain- and Blood-Brain Barrier-Associated Cell Types.
MedLine Citation:
PMID:  21935732     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Metal homeostasis is increasingly being evaluated as a therapeutic target in stroke and neurodegenerative diseases. Metal dysregulation has been shown to lead to protein aggregation, plaque formation and neuronal death. In 2007, we first reported that voltage-gated calcium channels act as a facile conduit for the entry of free ferrous (Fe(2+)) ions into neurons. Herein, we evaluate differential iron toxicity to central nervous system cells and assess the ability of the typical L-type voltage-gated calcium channel blocker nimodipine to attenuate iron-induced toxicity. The data demonstrate that iron sulfate induces a dose-dependent decrease in cell viability in rat brain endothelial cells (RBE4; LC(50) = 150 μM), neuronal cells (Neuro-2α neuroblastoma; LC(50) = 400 μM), and in astrocytes (DI TNC1; LC(50) = 1.1 mM). Pre-treatment with nimodipine prior to iron sulfate exposure provided a significant (P < 0.05) increase in viable cell numbers for RBE4 (2.5-fold), Neuro2-α (~2-fold), and nearly abolished toxicity in primary neurons. Astrocytes were highly resistant to iron toxicity compared to the other cell types tested and nimodipine had no (P > 0.05) protective effect in these cells. The data demonstrate variable susceptibility to iron overload conditions in different cell types of the brain and suggest that typical L-type voltage-gated calcium channel blockers (here represented by nimodipine), may serve as protective agents in conditions involving iron overload, particularly in cell types highly susceptible to iron toxicity.
Authors:
J A Lockman; W J Geldenhuys; K A Bohn; S F Desilva; D D Allen; C J Van der Schyf
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-21
Journal Detail:
Title:  Neurochemical research     Volume:  -     ISSN:  1573-6903     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7613461     Medline TA:  Neurochem Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Life, Earth, and Environmental Sciences, West Texas A&M University, 2403 Russell Long Blvd., Canyon, TX, 79016, USA, jlockman@wtamu.edu.
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