Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions

0575881 - ÚMG 2024 RIV CH eng J - Článek v odborném periodiku
Bugajev, Viktor - Dráberová, Lubica - Utekal, Pavol - Blažíková, Michaela - Tůmová, Magda - Dráber, Petr
Enhanced Membrane Fluidization and Cholesterol Displacement by 1-Heptanol Inhibit Mast Cell Effector Functions.
Cells. Roč. 12, č. 16 (2023), č. článku 2069. E-ISSN 2073-4409
Grant CEP: GA ČR(CZ) GA23-07736S; GA MŠMT LM2023052; GA MŠMT(CZ) LM2023050
Institucionální podpora: RVO:68378050
Klíčová slova: alkanol * membrane fluidizer * heat shock response * STIM1-ORAI1 coupling * store-operated calcium entry * Fc epsilon RI signaling * flow-FRET * frap
Obor OECD: Cell biology
Impakt faktor: 6, rok: 2022
Způsob publikování: Open access
https://www.mdpi.com/2073-4409/12/16/2069

Signal transduction by the high-affinity IgE receptor (Fc epsilon RI) depends on membrane lipid and protein compartmentalization. Recently published data show that cells treated with 1-heptanol, a cell membrane fluidizer, exhibit changes in membrane properties. However, the functional consequences of 1-heptanol-induced changes on mast cell signaling are unknown. This study shows that short-term exposure to 1-heptanol reduces membrane thermal stability and dysregulates mast cell signaling at multiple levels. Cells treated with 1-heptanol exhibited increased lateral mobility and decreased internalization of the Fc epsilon RI. However, this did not affect the initial phosphorylation of the Fc epsilon RI-beta chain and components of the SYK/LAT1/PLC gamma 1 signaling pathway after antigen activation. In contrast, 1-heptanol inhibited SAPK/JNK phosphorylation and effector functions such as calcium response, degranulation, and cytokine production. Membrane hyperfluidization induced a heat shock-like response via increased expression of the heat shock protein 70, increased lateral diffusion of ORAI1-mCherry, and unsatisfactory performance of STIM1-ORAI1 coupling, as determined by flow-FRET. Furthermore, 1-heptanol inhibited the antigen-induced production of reactive oxygen species and potentiated stress-induced plasma membrane permeability by interfering with heat shock protein 70 activity. The combined data suggest that 1-heptanol-mediated membrane fluidization does not interfere with the earliest biochemical steps of Fc epsilon RI signaling, such as phosphorylation of the Fc epsilon RI-beta chain and components of the SYK/LAT/PLC gamma 1 signaling pathway, instead inhibiting the Fc epsilon RI internalization and mast cell effector functions, including degranulation and cytokine production.
Trvalý link: https://hdl.handle.net/11104/0345588