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.
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Authors | Simona Magi, Pasqualina Castaldo, Giuseppina Carrieri, Antonella Scorziello, Gianfranco Di Renzo, Salvatore Amoroso |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 315
Issue 1
Pg. 291-6
(Oct 2005)
ISSN: 0022-3565 [Print] United States |
PMID | 16009740
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 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
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Topics |
- 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, physiology)
- Thiourea
(analogs & derivatives, pharmacology)
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