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TOXICOLOGY

Involvement of Na⁺-Ca²⁺ Exchanger in Intracellular Ca²⁺ Increase and Neuronal Injury Induced by Polychlorinated Biphenyls in Human Neuroblastoma SH-SY5Y Cells

Department of Neuroscience, Unit of Pharmacology, School of Medicine, University "Politecnica delle Marche," Ancona, Italy (S.M., P.C., G.C., S.A.); and Unit of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples "Federico II", Naples, Italy (A.S., G.D.R.)

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.

Address correspondence to: Prof. Salvatore Amoroso, Department of Neuroscience, Unit of Pharmacology, School of Medicine, University "Politecnica delle Marche", Via Tronto 10/A, 60020 Torrette, Ancona, Italy. E-mail: s.amoroso{at}univpm.it

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