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Open access
Life Sciences, volume 288, pages 120174

Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2

Pavlyuchenkova Anastasia N
Makievskaya Ciara I 1, 2, 3
Galkin Ivan I.
Chelombitko Maria A 4
Zinovkin Roman A.
Зиновкин Р. А. 4
Galkin Ivan 4
Publication typeJournal Article
Publication date2022-01-01
Journal: Life Sciences
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor6.1
ISSN00243205, 18790631
General Biochemistry, Genetics and Molecular Biology
General Medicine
General Pharmacology, Toxicology and Pharmaceutics
Abstract
FcεRI-dependent activation and degranulation of mast cells (MC) play an important role in allergic diseases. We have previously demonstrated that triphenylphosphonium (TPP)-based antioxidant SkQ1 inhibits mast cell degranulation, but the exact mechanism of this inhibition is still unknown. This study focused on investigating the influence of TPP-based compounds SkQ1 and C12TPP on FcεRI-dependent mitochondrial dysfunction and signaling during MC degranulation.MC were sensitized by anti-dinitrophenyl IgE and stimulated by BSA-conjugated dinitrophenyl. The degranulation of MC was estimated by β-hexosaminidase release. The effect of TPP-based compounds on FcεRI-dependent signaling was determined by Western blot analysis for adapter molecule LAT, kinases Syk, PI3K, Erk1/2, and p38. Fluorescent microscopy was used to evaluate mitochondrial parameters such as morphology, membrane potential, reactive oxygen species and ATP level.Pretreatment with TPP-based compounds significantly decreased FcεRI-dependent degranulation of MC. TPP-based compounds also prevented mitochondrial dysfunction (drop in mitochondrial ATP level and mitochondrial fission), and decreased Erk1/2 kinase phosphorylation. Selective Erk1/2 inhibition by U0126 also reduced β-hexosaminidase release and prevented mitochondrial fragmentation during FcεRI-dependent degranulation of MC.These findings expand the fundamental understanding of the role of mitochondria in the activation of MC. It also contributes to the rationale for the development of mitochondrial-targeted drugs for the treatment of allergic diseases.

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Pavlyuchenkova A. N. et al. Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2 // Life Sciences. 2022. Vol. 288. p. 120174.
GOST all authors (up to 50) Copy
Pavlyuchenkova A. N., Makievskaya C. I., Galkin I. I., Chelombitko M. A., Zinovkin R. A., Зиновкин Р. А., Galkin I. Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2 // Life Sciences. 2022. Vol. 288. p. 120174.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1016/j.lfs.2021.120174
UR - https://doi.org/10.1016%2Fj.lfs.2021.120174
TI - Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2
T2 - Life Sciences
AU - Pavlyuchenkova, Anastasia N
AU - Makievskaya, Ciara I
AU - Galkin, Ivan I.
AU - Chelombitko, Maria A
AU - Zinovkin, Roman A.
AU - Зиновкин, Р. А.
AU - Galkin, Ivan
PY - 2022
DA - 2022/01/01 00:00:00
PB - Elsevier
SP - 120174
VL - 288
SN - 0024-3205
SN - 1879-0631
ER -
BibTex
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BibTex Copy
@article{2022_Pavlyuchenkova
author = {Anastasia N Pavlyuchenkova and Ciara I Makievskaya and Ivan I. Galkin and Maria A Chelombitko and Roman A. Zinovkin and Р. А. Зиновкин and Ivan Galkin},
title = {Mitochondria-targeted triphenylphosphonium-based compounds inhibit FcεRI-dependent degranulation of mast cells by preventing mitochondrial dysfunction through Erk1/2},
journal = {Life Sciences},
year = {2022},
volume = {288},
publisher = {Elsevier},
month = {jan},
url = {https://doi.org/10.1016%2Fj.lfs.2021.120174},
pages = {120174},
doi = {10.1016/j.lfs.2021.120174}
}
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