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Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line : proliferating versus neuron-like cells

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Abstract
Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer's disease or Parkinson's disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, subsequently, Cu isotopic analysis was performed at cellular and sub-cellular levels via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). The SH-SY5Y cells showed a re-distribution of intracellular Cu upon RA differentiation. Both undifferentiated and differentiated cells became systematically enriched in the light Cu-63 isotope with increasing intracellular Cu content. Differentiated neuron-like SH-SY5Y cells showed a heavier Cu isotopic composition (+0.3) than did the undifferentiated proliferating cells when exposed to Cu for 24h. However, after a longer exposure time (72h), no difference was observed between both cellular phenotypes. Mitochondrial fractions were enriched in the light Cu-63 isotope, compared to whole cells, for both undifferentiated and differentiated cells (no significant difference). The Cu isotopic composition of the remaining cell lysates was heavier than that of the whole cells and +0.2 heavier in the differentiated cells than in the undifferentiated cells. These results indicate that neuronal differentiation affects the Cu isotope fractionation accompanying Cu uptake in the cells, but this effect does not seem to be associated with the mitochondrial Cu pathway. Cu isotope fractionation can be an interesting tool for studying Cu metabolism at a (sub)-cellular level in functional neurons.
Keywords
SH-SY5Y cell line, Retinoic acid differentiation, Cu spatial distribution, Cu isotope fractionation, LA-ICP-MS, MC-ICP-MS, ACID-INDUCED DIFFERENTIATION, ICP-MASS SPECTROMETRY, RETINOIC ACID, HEPATOCELLULAR-CARCINOMA, SIGNALING PATHWAY, BLOOD-SERUM, COPPER, MITOCHONDRIA, TARGET

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MLA
Costas Rodriguez, Marta et al. “Cellular and Sub-cellular Cu Isotope Fractionation in the Human Neuroblastoma SH-SY5Y Cell Line : Proliferating Versus Neuron-like Cells.” Ed. Erin Baker et al. ANALYTICAL AND BIOANALYTICAL CHEMISTRY 411.19 (2019): 4963–4971. Print.
APA
Costas Rodriguez, M., Colina Vegas, L., Solovyev, N., De Wever, O., & Vanhaecke, F. (2019). Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line : proliferating versus neuron-like cells. (E. Baker, K. Leopold, F. Ricci, & W. Wang, Eds.)ANALYTICAL AND BIOANALYTICAL CHEMISTRY, 411(19), 4963–4971.
Chicago author-date
Costas Rodriguez, Marta, Legna Colina Vegas, Nikolay Solovyev, Olivier De Wever, and Frank Vanhaecke. 2019. “Cellular and Sub-cellular Cu Isotope Fractionation in the Human Neuroblastoma SH-SY5Y Cell Line : Proliferating Versus Neuron-like Cells.” Ed. Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang. Analytical and Bioanalytical Chemistry 411 (19): 4963–4971.
Chicago author-date (all authors)
Costas Rodriguez, Marta, Legna Colina Vegas, Nikolay Solovyev, Olivier De Wever, and Frank Vanhaecke. 2019. “Cellular and Sub-cellular Cu Isotope Fractionation in the Human Neuroblastoma SH-SY5Y Cell Line : Proliferating Versus Neuron-like Cells.” Ed. Erin Baker, Kerstin Leopold, Francesco Ricci, and Wei Wang. Analytical and Bioanalytical Chemistry 411 (19): 4963–4971.
Vancouver
1.
Costas Rodriguez M, Colina Vegas L, Solovyev N, De Wever O, Vanhaecke F. Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line : proliferating versus neuron-like cells. Baker E, Leopold K, Ricci F, Wang W, editors. ANALYTICAL AND BIOANALYTICAL CHEMISTRY. 2019;411(19):4963–71.
IEEE
[1]
M. Costas Rodriguez, L. Colina Vegas, N. Solovyev, O. De Wever, and F. Vanhaecke, “Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line : proliferating versus neuron-like cells,” ANALYTICAL AND BIOANALYTICAL CHEMISTRY, vol. 411, no. 19, pp. 4963–4971, 2019.
@article{8617989,
  abstract     = {Cu isotope fractionation was investigated in the human neuroblastoma SH-SY5Y cell line, in a proliferating/tumor phase (undifferentiated cells), and in a differentiated state (neuron-like cells), induced using retinoic acid (RA). The SH-SY5Y cell line displays genetic aberrations due to its cancerous origin, but differentiation drives the cell line towards phenotypes suitable for the research of neurological diseases (e.g., Alzheimer's disease or Parkinson's disease). Cellular Cu distribution was first explored by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging and, subsequently, Cu isotopic analysis was performed at cellular and sub-cellular levels via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS). The SH-SY5Y cells showed a re-distribution of intracellular Cu upon RA differentiation. Both undifferentiated and differentiated cells became systematically enriched in the light Cu-63 isotope with increasing intracellular Cu content. Differentiated neuron-like SH-SY5Y cells showed a heavier Cu isotopic composition (+0.3) than did the undifferentiated proliferating cells when exposed to Cu for 24h. However, after a longer exposure time (72h), no difference was observed between both cellular phenotypes. Mitochondrial fractions were enriched in the light Cu-63 isotope, compared to whole cells, for both undifferentiated and differentiated cells (no significant difference). The Cu isotopic composition of the remaining cell lysates was heavier than that of the whole cells and +0.2 heavier in the differentiated cells than in the undifferentiated cells. These results indicate that neuronal differentiation affects the Cu isotope fractionation accompanying Cu uptake in the cells, but this effect does not seem to be associated with the mitochondrial Cu pathway. Cu isotope fractionation can be an interesting tool for studying Cu metabolism at a (sub)-cellular level in functional neurons.},
  author       = {Costas Rodriguez, Marta and Colina Vegas, Legna and Solovyev, Nikolay and De Wever, Olivier and Vanhaecke, Frank},
  editor       = {Baker, Erin and Leopold, Kerstin and Ricci, Francesco and Wang, Wei},
  issn         = {1618-2642},
  journal      = {ANALYTICAL AND BIOANALYTICAL CHEMISTRY},
  keywords     = {SH-SY5Y cell line,Retinoic acid differentiation,Cu spatial distribution,Cu isotope fractionation,LA-ICP-MS,MC-ICP-MS,ACID-INDUCED DIFFERENTIATION,ICP-MASS SPECTROMETRY,RETINOIC ACID,HEPATOCELLULAR-CARCINOMA,SIGNALING PATHWAY,BLOOD-SERUM,COPPER,MITOCHONDRIA,TARGET},
  language     = {eng},
  number       = {19},
  pages        = {4963--4971},
  title        = {Cellular and sub-cellular Cu isotope fractionation in the human neuroblastoma SH-SY5Y cell line : proliferating versus neuron-like cells},
  url          = {http://dx.doi.org/10.1007/s00216-019-01871-6},
  volume       = {411},
  year         = {2019},
}

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