Background ATP7A, ATP7B and CTR1 are steel transporting proteins that control the cellular disposition of copper and platinum drugs, but their expression in dorsal root ganglion (DRG) tissue and their role in platinum-induced neurotoxicity are unknown. neurons without co-localization with ATP7A. DRG neurons with strong expression of ATP7A or CTR1 buy Oxymatrine (Matrine N-oxide) experienced unique cell body size profiles with minimal overlap between them. Oxaliplatin treatment did not alter the size profile of strongly ATP7A-immunoreactive neurons but significantly reduced the size profile of strongly CTR1-immunoreactive neurons. ATP7B mRNA was barely detectable, and no specific immunoreactivity for ATP7B was found, in DRG tissue from healthy control animals. Conclusions In conclusion, adult rat DRG tissue exhibits a specific pattern of expression of copper transporters with distinct subsets of peripheral sensory neurons intensely expressing either ATP7A or CTR1, but not both or ATP7B. The neuron subtype-specific and largely non-overlapping distribution of ATP7A and CTR1 within rat DRG tissue may be required to support the potentially differing cuproenzyme requirements of unique subsets of sensory neurons, and could influence the transport and neurotoxicity buy Oxymatrine (Matrine N-oxide) of oxaliplatin. Background ATP7A, ATP7B and CTR1 are copper transporting proteins that have evolved along with other components of copper regulatory pathways for delivering copper to Rabbit Polyclonal to FBLN2 essential cuproenzymes without releasing highly cytotoxic free copper ions [1,2]. The P-type ATPases, ATP7A and ATP7B, both transport copper out of cells or into the trans-Golgi network , whereas CTR1 is usually a plasma membrane protein that functions as a high-affinity cellular copper uptake transporter . ATP7A, ATP7B and CTR1 exhibit cell-type specific expression in the brain and other tissues [5,6], reflecting buy Oxymatrine (Matrine N-oxide) their requirements for copper to support the functions of diverse cuproenzymes, such as dopamine–monooxygenase and peptidylglycine -amidating monooxygenase that convert dopamine to norepinephrine and buy Oxymatrine (Matrine N-oxide) synthesize neuropeptides, respectively . Disturbance of copper transporters causes neurodegeneration. For example, mutation of ATP7A and ATP7B causes Menkes and Wilson disease, respectively, both of which have severe neurological sequelae including mental retardation, seizures, developmental delay and ataxia . Little is currently known about the expression of copper transporters in the dorsal root ganglia (DRG) that contain the cell body of main sensory neurons. These neurons may require copper transport as they strongly express cuproenzymes, such as cytochrome C oxidase , Cu/Zn superoxide dismutase  and peptidylglycine -amidating monooxygenase , and are sensitive to copper deficiency [11,12]. In other cell types, copper transporters have been shown to have a role in controlling the cellular accumulation and cytotoxicity of platinum drugs, with CTR1 mediating platinum uptake into cells [13-15], and ATP7A and ATP7B transporting platinum out of cells or into specific sub-cellular compartments [16-20]. Platinum-based drugs, such as cisplatin and oxaliplatin, accumulate in DRG tissue [21-26], damage sensory neurons [21,22,24-33], and induce peripheral sensory neuropathies that limit their use in clinical malignancy chemotherapy . In the current study, we investigated the expression of ATP7A, ATP7B and CTR1 in DRG tissue from adult rats, either healthy control animals or those treated with oxaliplatin or its drug vehicle. Neuronal atrophy was used as the endpoint for measuring the neurotoxicity of oxaliplatin in DRG tissues, as in previous studies [26,29,35-37]. We aimed to determine patterns of expression and localization of ATP7A and ATP7B within DRG tissue, in an extension to our recent study of CTR1 , and to relate the expression of these copper transporters to the neurotoxicity of oxaliplatin. Results Copper transporter gene expression in DRG and other tissues The expression of copper transporter genes in rat DRG tissue was determined by RT-PCR and qPCR in comparison to reference tissues (brain, spinal cord, liver, kidney and intestine). The RT-PCR (Physique ?(Determine1)1) and qPCR (Table ?(Table1)1) findings corresponded buy Oxymatrine (Matrine N-oxide) well with each other. In all of the.