@article {Magi291, author = {Simona Magi and Pasqualina Castaldo and Giuseppina Carrieri and Antonella Scorziello and Gianfranco Di Renzo and Salvatore Amoroso}, title = {Involvement of Na+-Ca2+ Exchanger in Intracellular Ca2+ Increase and Neuronal Injury Induced by Polychlorinated Biphenyls in Human Neuroblastoma SH-SY5Y Cells}, volume = {315}, number = {1}, pages = {291--296}, year = {2005}, doi = {10.1124/jpet.105.088948}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/315/1/291}, eprint = {https://jpet.aspetjournals.org/content/315/1/291.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }