Correlative Cellular Mass Spectrometry Imaging and Amperometry Show Dose Dependent Changes in Lipid Composition and Exocytosis.

Amperometry Lipidomics Proteasomal Inhibition Single-Cell ToF-SIMS

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
03 04 2023
Historique:
received: 06 12 2022
medline: 28 3 2023
pubmed: 8 2 2023
entrez: 7 2 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36749546
doi: 10.1002/anie.202217993
doi:

Substances chimiques

lactacystin 133343-34-7
Proteasome Inhibitors 0
Membrane Lipids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202217993

Informations de copyright

© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Inci Barut (I)

Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Gothenburg, Sweden.
Current address: Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Gazi University, Ankara, Turkey.

Xiulan He (X)

Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Gothenburg, Sweden.

Erol Sener (E)

Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir, Turkey.

Sanna Sämfors (S)

Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Gothenburg, Sweden.

Andrew G Ewing (AG)

Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Gothenburg, Sweden.

John S Fletcher (JS)

Department of Chemistry and Molecular Biology, University of Gothenburg, 41296, Gothenburg, Sweden.

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