Copper Acetate Manufacturers(WSDTY) proposed the Copper Acetate results of fluorescence imaging and ICP-MS are concrete evidence that PC12 cells specifically accumulated Cu in cytoplasm. Although intracellular Cu concentration was increased, the mRNA and protein expressions of Ctr1, a Cu influx transporter, was decreased by the differentiation. Indeed, the fact that the differentiated cells showed higher tolerance to Ctr1 substrate than the naive cells. It has been pointed out that Ctr1 is controlled not at the transcriptional level but at the post-translational level depending on the Cu concentration around cells27. Ctr1 protein is localized stably on the plasma membrane under the Cu-depleted condition, but loses intracellular stability under the Cu-replete condition28. In this study, Crt1 showed decreases in functional and transcriptional activities and hence, it was concluded that the Ctr1 expression was decreased by the differentiation of PC12 cells into neurons at the transcription level. Based on this scenario, a discrepancy would be expected regarding the intracellular Cu concentration: if Ctr1 expression were decreased by the differentiation, intracellular Cu concentration would be decreased.
However, as mentioned above, this study and a previous study indicated that the intracellular Cu concentration was increased by the differentiation26. Thus, we speculated that during the differentiation process, the PC12 cells initially accumulated Cu and then decreased Ctr1 expression. In other words, the differentiation of PC12 cells induced the Cu accumulation and, with the intent of ameliorating the Cu accumulation, Ctr1 expression in the differentiated cells was decreased. Then we ask, why and how do PC12 cells accumulate Cu during differentiation? We speculate that MT-3 plays a role in the differentiation of PC12 cells into neurons.
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