Differential Effect Of Nimodipine In Attenuating Iron-induced Toxicity In Brain- And Blood-brain Barrier-associated Cell Types

Title

Differential Effect Of Nimodipine In Attenuating Iron-induced Toxicity In Brain- And Blood-brain Barrier-associated Cell Types

Creator

Lockman J A; Geldenhuys W J; Bohn K A; DeSilva S F; Allen D D; Van der Schyf C J

Publisher

Neurochemical Research

Date

2012
2012-01

Description

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 (Fe2+) 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; LC50 = 150 mu M), neuronal cells (Neuro-2 alpha neuroblastoma; LC50 = 400 mu M), and in astrocytes (DI TNC1; LC50 = 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-alpha (similar to 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.

Subject

Astrocytes; Biochemistry & Molecular Biology; central-nervous-system; cerebrospinal-fluid; cultured astrocytes; intracerebral hemorrhage; Iron in brain; Metal toxicity; Neurodegenerative diseases; neurodegenerative disorders; neurons; Neurosciences & Neurology; Nimodipine; oxidative; parkinsons-disease; redox-active iron; stress; substantia-nigra; transferrin receptor; Vascular endothelial cells

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

134-142

Issue

1

Volume

37

Citation

Lockman J A; Geldenhuys W J; Bohn K A; DeSilva S F; Allen D D; Van der Schyf C J, “Differential Effect Of Nimodipine In Attenuating Iron-induced Toxicity In Brain- And Blood-brain Barrier-associated Cell Types,” NEOMED Bibliography Database, accessed April 14, 2021, https://neomed.omeka.net/items/show/10785.

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