Involvement of Na+-Ca2+ exchanger in intracellular Ca2+ increase and neuronal injury induced by polychlorinated biphenyls in human neuroblastoma SH-SY5Y cells.
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.
Magi
Simona
S
Department of Neuroscience, Unit of Pharmacology, School of Medicine, University Politecnica delle Marche, Ancona, Italy.
Castaldo
Pasqualina
P
Carrieri
Giuseppina
G
Scorziello
Antonella
A
Di Renzo
Gianfranco
G
Amoroso
Salvatore
S
D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D026901:Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C101832:SLC38A3 protein, human; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D020111:Chlorodiphenyl (54% Chlorine); D015764:Bepridil; D013890:Thiourea; D002118:Calcium