Abstract
Suramin is an experimental chemotherapeutic agent and a neurotoxin which causes a dose-dependent peripheral neuropathy in vivo and inhibits dorsal root ganglion (DRG) neurite outgrowth in vitro. The mechanism of suramin-induced cyto- and neurotoxicity remains unclear. Calcium is a key signal transducer in cellular responses to a variety of physiological and pathogenic stimuli. In the present study, we have determined the role of calcium in suramin-induced neurotoxicity in dorsal root ganglion neurons in vitro. Suramin-induced inhibition of neurite outgrowth and induction of neuronal cell death were dose-related phenomena. A low level of extracellular calcium significantly reduced suramin-induced inhibition of neurite outgrowth and delayed neuronal cell death in vitro. Nimodipine (100 μM), an L-type voltage-sensitive calcium channel (VSCC) inhibitor, mimicked low calcium medium and protected neurite outgrowth in regular calcium medium supplemented with 300 μM suramin. TMB-8 (100 μM), an inhibitor of intracellular calcium release, failed to protect neurite outgrowth against the toxin. Calmidazolium (10 μM), a potent calmodulin inhibitor, and calpain inhibitor peptide (CIP, 10 μM) protected neurite outgrowth against suramin. The results support the hypothesis that the calcium signaling system is important in suramin-induced neurotoxicity. Influx of extracellular calcium is more important than release of intracellular calcium in causing cell injury in vitro.
Original language | English (US) |
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Pages (from-to) | 149-156 |
Number of pages | 8 |
Journal | Brain Research |
Volume | 742 |
Issue number | 1-2 |
DOIs | |
State | Published - Dec 2 1996 |
Keywords
- calcium
- calpain
- dorsal root ganglia
- neurite outgrowth
- neurotoxicity
- suramin
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology