Molecular Biology Reports, volume 50, issue 3, pages 2317-2333

Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats

Tregub Pavel 1, 2
Malinovskaya Natalia 1
Hilazheva Elena 1
Morgun Andrey 1
Kulikov Vladimir 3, 4
Publication typeJournal Article
Publication date2022-12-28
Quartile SCImago
Q2
Quartile WOS
Q3
Impact factor2.8
ISSN03014851, 15734978
Molecular Biology
General Medicine
Genetics
Abstract
In the present study, we aimed to test the hypothesis that hypercapnia, independently and/or in combination with hypoxia, can activate signaling pathways related to the inhibition of proapoptotic (caspase-dependent and caspase-independent) factors and the induction of antiapoptotic factors in facilitating adaptation to hypoxia/ischemia. Following exposure to permissive hypercapnia and/or normobaric hypoxia, the degree of apoptosis was evaluated in experimental ischemia models in vivo and in vitro. The percentages of caspase-3, apoptosis-inducing factor (AIF), Bax, and Bcl-2 in astrocytes and neurons derived from male Wistar rats were also calculated. In vitro, cells were subjected to various types of respiratory exposure (hypoxia and/or hypercapnia for 24 or 12 h) as well as further sublethal chemical hypoxia. The percentages of these molecules in nerve cells in the ischemic penumbra of the brain after photothrombotic injury were also calculated. The degree of apoptosis was found to decrease in ischemic penumbra, mostly due to the hypercapnic component. It was also discovered that the levels of caspase-3, AIF, and Bax decreased in this region, whereas the Bcl-2 levels increased following exposure to hypercapnia and hypercapnic hypoxia. This integrative assessment of the rate of apoptosis/necrosis in astrocyte and neuron cultures shows that the combination of hypercapnia and hypoxia resulted in the maximum neuroprotective effect. The levels of apoptosis mediators in astrocyte and neuron cultures were calculated after modeling chemical hypoxia in vitro. These results show that the exposure models where permissive hypercapnia and normobaric hypoxia were combined also had the most pronounced inhibitory effects on apoptotic signaling pathways.

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Tregub P. et al. Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats // Molecular Biology Reports. 2022. Vol. 50. No. 3. pp. 2317-2333.
GOST all authors (up to 50) Copy
Tregub P., Malinovskaya N., Hilazheva E., Morgun A., Kulikov V. Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats // Molecular Biology Reports. 2022. Vol. 50. No. 3. pp. 2317-2333.
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TY - JOUR
DO - 10.1007/s11033-022-08212-4
UR - https://doi.org/10.1007%2Fs11033-022-08212-4
TI - Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats
T2 - Molecular Biology Reports
AU - Tregub, Pavel
AU - Malinovskaya, Natalia
AU - Hilazheva, Elena
AU - Morgun, Andrey
AU - Kulikov, Vladimir
PY - 2022
DA - 2022/12/28 00:00:00
PB - Springer Nature
SP - 2317-2333
IS - 3
VL - 50
SN - 0301-4851
SN - 1573-4978
ER -
BibTex |
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@article{2022_Tregub,
author = {Pavel Tregub and Natalia Malinovskaya and Elena Hilazheva and Andrey Morgun and Vladimir Kulikov},
title = {Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats},
journal = {Molecular Biology Reports},
year = {2022},
volume = {50},
publisher = {Springer Nature},
month = {dec},
url = {https://doi.org/10.1007%2Fs11033-022-08212-4},
number = {3},
pages = {2317--2333},
doi = {10.1007/s11033-022-08212-4}
}
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Tregub, Pavel, et al. “Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats.” Molecular Biology Reports, vol. 50, no. 3, Dec. 2022, pp. 2317-2333. https://doi.org/10.1007%2Fs11033-022-08212-4.
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