Involvement of Na+-Ca2+ exchanger in intracellular Ca2+ increase and neuronal injury induced by polychlorinated biphenyls in human neuroblastoma SH-SY5Y cells

J Pharmacol Exp Ther. 2005 Oct;315(1):291-6. doi: 10.1124/jpet.105.088948. Epub 2005 Jul 11.

Abstract

In SH-SY5Y, a human neuroblastoma cell line, Aroclor 1254 (A1254), induced a dose-dependent (10-50 microg/ml) intracellular calcium concentration ([Ca2+]i) increase. Two rather specific sodium-calcium (Na+-Ca2+) exchanger (NCX) inhibitors, bepridil (10 microM) and KB-R7943 [2-[2-[4-(4-nitrobenzyloxy) phenyl]ethyl]isothiourea methanesulfonate] (10 microM), reduced A1254-induced [Ca2+]i increase. A 24-h exposure to 30 microg/ml A1254 caused remarkable SH-SY5Y neuroblastoma cell damage. It is noteworthy that both bepridil and KB-R7943 counteracted A1254-induced neuronal injury. These results indicate that NCX contributes to [Ca2+]i increase and neuronal injury induced by A1254. RT-PCR experiments revealed in SH-SY5Y neuroblastoma cells the expression of NCX1 and NCX3 isoforms. To investigate which isoform was involved in [Ca2+]i increase and neuronal damage induced by A1254, we used specific antisense oligodeoxynucleotides (ODNs) to reduce NCX1 or NCX3 protein expression. The results showed that only NCX1 ODN reduced [Ca2+]i increase and neuronal injury induced by A1254. In conclusion, these results indicate that NCX1 may participate to [Ca2+]i increase and neurotoxicity evoked by A1254 in SH-SY5Y neuroblastoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bepridil / pharmacology
  • Calcium / metabolism*
  • Cell Line, Tumor
  • Chlorodiphenyl (54% Chlorine) / toxicity*
  • Humans
  • Membrane Transport Proteins / physiology
  • Neurons / drug effects*
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / analysis
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / physiology*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology

Substances

  • 2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate
  • Membrane Transport Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • SLC38A3 protein, human
  • Sodium-Calcium Exchanger
  • sodium-calcium exchanger 1
  • Chlorodiphenyl (54% Chlorine)
  • Bepridil
  • Thiourea
  • Calcium