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Neuronal expression of copper transporter 1 in rat dorsal root ganglia: association with platinum neurotoxicity
Citation
Liu, JJ and Jamiesom, SMF and Subramaniam, J and Ip, V and Jong, NN and Mercer, JFB and McKeage, MJ, Neuronal expression of copper transporter 1 in rat dorsal root ganglia: association with platinum neurotoxicity, Cancer Chemotherapy and Pharmacology, 64, (4) pp. 847-856. ISSN 0344-5704 (2009) [Refereed Article]
Copyright Statement
Copyright 2009 Springer-Verlag
DOI: doi:10.1007/s00280-009-1017-6
Abstract
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 lm2) 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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | copper transporter 1, platinum neurotoxicity, dorsal root ganglion |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Clinical pharmacology and therapeutics |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Liu, JJ (Dr Johnson Liu) |
| ID Code: | 89121 |
| Year Published: | 2009 |
| Web of Science® Times Cited: | 48 |
| Deposited By: | Pharmacy |
| Deposited On: | 2014-02-25 |
| Last Modified: | 2014-05-19 |
| Downloads: | 0 |
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