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Changes in intracellular copper concentration and copper-regulating gene expression after PC12 differentiation into
Yasumitsu Ogra1,2, Aya Tejima2, Naohiro Hatakeyama2
1Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba 260-8675, Japan.
Scientific Reports
|September 14, 2016
Summary
Neuronal differentiation increases intracellular copper (Cu) levels by upregulating metallothionein-3 (MT-3) and decreasing the copper transporter Ctr1. This suggests a role for copper homeostasis in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Disturbances in copper (Cu) homeostasis are implicated in neurodegenerative diseases.
- The specific effects of altered Cu homeostasis on neurons are not fully understood.
Purpose of the Study:
- To investigate copper metabolism in neurons.
- To examine changes in intracellular Cu concentration and Cu-regulating gene expression during neuronal differentiation.
Main Methods:
- Used rat pheochromocytoma (PC12) cells differentiated into neurons.
- Employed fluorescent probes for Cu and Zn imaging.
- Utilized inductively coupled plasma mass spectrometry for metal analysis.
- Analyzed mRNA expression of copper transporters and metallothioneins (MTs).
Main Results:
- Neuronal differentiation increased intracellular Cu concentration.
- Expression of the Cu influx transporter Ctr1 decreased post-differentiation.
- Metallothionein-3 (MT-3) expression, a brain-specific isoform, increased, while MT-1 and MT-2 decreased.
- Differentiated cells showed tolerance to Cu and cisplatin.
Conclusions:
- PC12 cell differentiation into neurons leads to intracellular Cu accumulation.
- Increased MT-3 expression and decreased Ctr1 expression are key mechanisms in neuronal Cu homeostasis.
- These findings provide insights into the role of copper in neuronal function and neurodegeneration.
