Correlative Cellular Mass Spectrometry Imaging and Amperometry Show Dose Dependent Changes in Lipid Composition and Exocytosis. (28th February 2023)

• Record Type: Journal Article
• Authors: Barut, Inci; He, Xiulan; Sener, Erol; Sämfors, Sanna; Ewing, Andrew G.; Fletcher, John S.
• Is Part Of: Angewandte Chemie. Volume 135:Number 15(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-28
• Subjects: Amperometry -- Lipidomics -- Proteasomal Inhibition -- Single-Cell -- ToF-SIMS; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202217993
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Aberrant functioning of the proteasome has been associated with crucial pathologic conditions including neurodegeneration. Yet, the complex underlying causes at the cellular level remain unclear and there are conflicting reports of neuroprotective to neurodegenerative effects of proteasomal inhibitors such as lactacystin that are utilised as models for neurodegenerative diseases. The conflicting results may be associated with different dose regimes of lactacystin and hence we have performed a dose dependent study of the effects of lactacystin to identify concurrent changes in the cell membrane lipid profile and the dynamics of exocytosis using a combination of surface sensitive mass spectrometry and single cell amperometry. Significant changes of negatively charged lipids were associated with different lactacystin doses that showed a weak correlation with exocytosis while changes in PE and PE−O lipids showed dose dependent changes correlated with initial pore formation and total release of vesicle content respectively. Abstract : Novel analytical tools — single cell amperometry (SCA ), intracellular vesicle impact electrochemical cytometry (IVIEC ), and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS ) imaging — were combined to provide a link between the complex etiology of neurodegenerative diseases and lipidomic information.