Changes in intracellular copper concentration and copper-regulating gene expression after PC12 differentiation into neurons
| Autor: | Yasumi Anan, Yasumitsu Ogra, Siyuan Wu, Aya Tejima, Tsutomu Ishikawa, Noriyuki Suzuki, Ayako Yawata, Moeko Shiraiwa, Naohiro Hatakeyama |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene isoform Cellular differentiation Gene Expression Nerve Tissue Proteins Biology PC12 Cells Article 03 medical and health sciences Gene expression Animals Homeostasis RNA Messenger Cation Transport Proteins Gene Copper Transporter 1 Neurons Multidisciplinary Cell Differentiation Transporter Metabolism Molecular biology Metallothionein 3 Rats Cell biology Zinc 030104 developmental biology Metals Metallothionein Copper Intracellular |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep33007 |
| Popis: | It is suspected that some neurodegenerative diseases are a result of the disturbance of copper (Cu) homeostasis, although it remains unclear whether the disturbance of Cu homeostasis has aberrant effects on neurons. Herein, we investigated Cu metabolism specifically in neurons in terms of changes in the intracellular Cu concentration and the expression of Cu-regulating genes, such as Cu transporters and metallothioneins (MTs), before and after the differentiation of rat pheochromocytoma cells (PC12 cells) into neurons. After the differentiation, Cu and Zn imaging with fluorescent probes revealed an increase in intracellular Cu concentration. The concentrations of other essential metals, which were determined by an inductively coupled plasma mass spectrometer, were not altered. The mRNA expression of the Cu influx transporter, Ctr1, was decreased after the differentiation, and the differentiated cells acquired tolerance to Cu and cisplatin, another substrate of Ctr1. In addition, the expression of MT-3, a brain-specific isoform, was increased, contrary to the decreased expression of MT-1 and MT-2. Taken together, the differentiation of PC12 cells into neurons induced MT-3 expression, thereby resulting in intracellular Cu accumulation. The decrease in Ctr1 expression was assumed to be a response aimed at abolishing the physiological accumulation of Cu after the differentiation. |
| Databáze: | OpenAIRE |
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