Calcium in suramin-induced rat sensory neuron toxicity in vitro

Sun Xiaofeng, Anthony J. Windebank

Research output: Contribution to journalArticle

19 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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