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Mass Spectrometry Imaging Suggests That Cisplatin Affects Exocytotic Release by Alteration of Cell Membrane Lipids

Artikel i vetenskaplig tidskrift
Författare Amir Saeid Mohammadi
Xianchan Li
Andrew G Ewing
Publicerad i Analytical Chemistry
Volym 90
Nummer/häfte 14
Sidor 8509-8516
ISSN 0003-2700
Publiceringsår 2018
Publicerad vid Institutionen för kemi och molekylärbiologi
National Center for Imaging Mass Spectrometry
Sidor 8509-8516
Språk en
Länkar dx.doi.org/10.1021/acs.analchem.8b0...
Ämnesord laser-desorption ionization, cluster ion-beams, tof-sims, signal-transduction, alzheimers-disease, human fibroblasts, drosophila, brain, cancer-cells, cholesterol, transmitters, Chemistry
Ämneskategorier Analytisk kemi

Sammanfattning

We used time-of-flight secondary ion mass spectrometry (TOFSIMS) imaging to investigate the effect of cisplatin, the first member of the platinum-based anticancer drugs, on the membrane lipid composition of model cells to see if lipid changes might be involved in the changes in exocytosis observed. Platinum-based anticancer drugs have been reported to affect neurotransmitter release resulting in what is called the "chemobrain"; however, the mechanism for the influence is not yet understood. TOF-SIMS imaging was carried out using a high energy 40 keV (CO2)(6000)(+) gas cluster ion beam with improved sensitivity for intact lipids in biological samples. Principal components analysis showed that cisplatin treatment of PC12 cells significantly affects the abundance of different lipids and their derivatives, particularly phosphatidylcholine and cholesterol, which are diminished. Treatment of cells with 2 mu M and 100 mu M cisplatin showed similar effects on induced lipid changes. Lipid content alterations caused by cisplatin treatment at the cell surface are associated with the molecular and bimolecular signaling pathways of cisplatin-induced apoptosis of cells. We suggest that lipid alterations measured by TOF-SIMS are involved, at least in part, in the regulation of exocytosis by cisplatin.

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