RT Journal Article
SR Electronic
T1 Involvement of Na<sup>+</sup>-Ca<sup>2+</sup> Exchanger in Intracellular Ca<sup>2+</sup> Increase and Neuronal Injury Induced by Polychlorinated Biphenyls in Human Neuroblastoma SH-SY5Y Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 291
OP 296
DO 10.1124/jpet.105.088948
VO 315
IS 1
A1 Simona Magi
A1 Pasqualina Castaldo
A1 Giuseppina Carrieri
A1 Antonella Scorziello
A1 Gianfranco Di Renzo
A1 Salvatore Amoroso
YR 2005
UL http://jpet.aspetjournals.org/content/315/1/291.abstract
AB In SH-SY5Y, a human neuroblastoma cell line, Aroclor 1254 (A1254), induced a dose-dependent (10-50 μg/ml) intracellular calcium concentration ([Ca2+]i) increase. Two rather specific sodium-calcium (Na+-Ca2+) exchanger (NCX) inhibitors, bepridil (10 μM) and KB-R7943 [2-[2-[4-(4-nitrobenzyloxy) phenyl]ethyl]isothiourea methanesulfonate] (10 μM), reduced A1254-induced [Ca2+]i increase. A 24-h exposure to 30 μg/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. The American Society for Pharmacology and Experimental Therapeutics