Amir Saeid Mohammadi oral presentation (OB3-Tue3-1-2)
Cellular lipid membrane alterations induced by cisplatin measured using high energy gas cluster ion beam SIMS
1 University of Gothenburg - National center for imaging mass spectrometry, Kemigarden 4, 41296 Gothenburg, Sweden
2 University of Gothenburg - Department of Chemistry and Molecular Biology, , 40530 Gothenburg, Sweden
3 Chalmers University of Technology - Department of Chemistry and Chemical Engineering, , 41296 Gothenburg, Sweden
We utilized Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging to study the effect of cisplatin on the membrane lipid composition of PC12 cells to see if lipid changes might be involved in the changes in exocytosis and cognitive function observed during chemotherapy. Chemotherapy treatment has severe side effects such as nephrotoxicity, nausea, vomiting, ototoxicity and electrolyte disturbance. Chemotherapy can also cause mild cognitive impairment, known as the “chemobrain”, with symptoms such as difficulties with multitasking and focusing, memory lapses, and confusion [1, 2, 3]. Cisplatin as a platinum-based anti-cancer drug has been reported to affect the exocytosis of catecholamines, a series of central nervous system (CNS) neurotransmitters involved in neurological functions . Dynamic measurements of these the transmitters revealed that cisplatin alters dopamine release from single PC12 cells. However, the mechanism for the changes observed is not yet clear .
We applied a high-energy 40 keV (CO2)6000+ gas cluster beam as the primary ion source for ToF-SIMS imaging. This provided enhanced intensity for the detection of intact lipids in biological samples. Principal component analysis (PCA) showed that cisplatin treatment of PC12 cells dramatically affected the abundance of membrane lipids, particularly phosphatidyl choline (PC) and cholesterol. These lipid alterations can be involved, at least in part, in the regulation of exocytosis by cisplatin.
 B. Weiss, Neurotoxicology, 2008, 29, 891.
 N. Boykoff, M. Moieni and S. K. Subramanian, J. Cancer Surviv., 2009, 3, 223.
 S. Taillibert, D. Voillery and C. Bernard-Marty, Curr. Opin. Oncol., 2007, 19, 623.
 S. V. Kaplan, R. A. Limbocker, R. C. Gehringer, J. L. Divis, G. L. Osterhaus, M. D. Newby, M. J. Sofis, D. P. Jarmolowicz, B. D. Newman, T. A. Mathews and M. A. Johnson, ACS Chem. Neurosci., 2016, 7, 689.
 X. Li, J. Dunevall and A. G. Ewing, Angew. Chem. Int. Ed., 2016, 55, 9041.