Calcium in suramin-induced rat sensory neuron toxicity in vitro

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalBrain Research
Volume742
Issue number1-2
DOIs
StatePublished - Dec 2 1996

Fingerprint

Suramin
Sensory Receptor Cells
Calcium
Spinal Ganglia
calmidazolium
Cell Death
Nimodipine
Calcium Signaling
In Vitro Techniques
Neurotoxins
Peripheral Nervous System Diseases
Calmodulin
Calcium Channels
Transducers
Neuronal Outgrowth
Neurons
Wounds and Injuries

Keywords

  • calcium
  • calpain
  • dorsal root ganglia
  • neurite outgrowth
  • neurotoxicity
  • suramin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calcium in suramin-induced rat sensory neuron toxicity in vitro. / Xiaofeng, Sun; Windebank, Anthony John.

In: Brain Research, Vol. 742, No. 1-2, 02.12.1996, p. 149-156.

Research output: Contribution to journalArticle

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