Neuronal expression of copper transporter 1 in rat dorsal root ganglia: association with platinum neurotoxicity.
Cancer Chemother Pharmacol
; 64(4): 847-56, 2009 Sep.
Article
en En
| MEDLINE
| ID: mdl-19466412
ABSTRACT
PURPOSE:
We report the neuronal expression of copper transporter 1 (CTR1) in rat dorsal root ganglia (DRG) and its association with the neurotoxicity of platinum-based drugs.METHODS:
CTR1 expression was studied by immunohistochemistry and RT-PCR. The toxicity of platinum drugs to CTR1-positive and CTR1-negative neurons was compared in DRG from animals treated with maximum tolerated doses of oxaliplatin (1.85 mg/kg), cisplatin (1 mg/kg) or carboplatin (8 mg/kg) twice weekly for 8 weeks.RESULTS:
Abundant CTR1 mRNA was detected in DRG tissue. CTR1 immunoreactivity was associated with plasma membranes and cytoplasmic vesicular structures of a subpopulation (13.6 +/- 3.1%) of mainly large-sized (mean cell body area, 1,787 +/- 127 microm(2)) DRG neurons. After treatment with platinum drugs, the cell bodies of these CTR1-positive neurons became atrophied, with oxaliplatin causing the greatest percentage reduction in the mean cell body area relative to controls (42%; P < 0.05), followed by cisplatin (18%; P < 0.05) and carboplatin causing the least reduction (3.2%; P = NS). CTR1-negative neurons, with no immunoreactivity or only diffuse cytoplasmic staining, showed less treatment-induced cell body atrophy than CTR1-positive neurons.CONCLUSIONS:
CTR1 is preferentially expressed by a subset of DRG neurons that are particularly vulnerable to the toxicity of platinum drugs. These findings, together with its neuronal membrane localization, are suggestive of CTR1-related mechanisms of platinum drug neuronal uptake and neurotoxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Organoplatinos
/
Proteínas de Transporte de Catión
/
Ganglios Espinales
/
Neuronas
/
Antineoplásicos
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda