The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro

Ischemia-like (oxygen-glucose deprivation, OGD) conditions followed by reoxygenation (OGD/R) cause massive death of cerebral cortex cells in culture as a result of the induction of necrosis and apoptosis. Cell death occurs as a result of an OGD-induced increase in Ca<sup>2+</sup> ions in...

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Main Authors: Egor A. Turovsky, Elena G. Varlamova, Sergey V. Gudkov, Egor Y. Plotnikov
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/24/13216
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author Egor A. Turovsky
Elena G. Varlamova
Sergey V. Gudkov
Egor Y. Plotnikov
author_facet Egor A. Turovsky
Elena G. Varlamova
Sergey V. Gudkov
Egor Y. Plotnikov
author_sort Egor A. Turovsky
collection DOAJ
description Ischemia-like (oxygen-glucose deprivation, OGD) conditions followed by reoxygenation (OGD/R) cause massive death of cerebral cortex cells in culture as a result of the induction of necrosis and apoptosis. Cell death occurs as a result of an OGD-induced increase in Ca<sup>2+</sup> ions in the cytosol of neurons and astrocytes, an increase in the expression of genes encoding proapoptotic and inflammatory genes with suppression of protective genes. The deuterated form of linoleic polyunsaturated fatty acid (D4-Lnn) completely inhibits necrosis and greatly reduces apoptotic cell death with an increase in the concentration of fatty acid in the medium. It was shown for the first time that D4-Lnn, through the activation of the phosphoinositide calcium system of astrocytes, causes their reactivation, which correlates with the general cytoprotective effect on the cortical neurons and astrocytes in vitro. The mechanism of the cytoprotective action of D4-Lnn involves the inhibition of the OGD-induced calcium ions, increase in the cytosolic and reactive oxygen species (ROS) overproduction, the enhancement of the expression of protective genes, and the suppression of damaging proteins.
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spelling doaj.art-94d89567462b4947b73c2cfc7421258a2023-11-23T08:42:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241321610.3390/ijms222413216The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In VitroEgor A. Turovsky0Elena G. Varlamova1Sergey V. Gudkov2Egor Y. Plotnikov3Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaFederal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaProkhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove St., 119991 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, RussiaIschemia-like (oxygen-glucose deprivation, OGD) conditions followed by reoxygenation (OGD/R) cause massive death of cerebral cortex cells in culture as a result of the induction of necrosis and apoptosis. Cell death occurs as a result of an OGD-induced increase in Ca<sup>2+</sup> ions in the cytosol of neurons and astrocytes, an increase in the expression of genes encoding proapoptotic and inflammatory genes with suppression of protective genes. The deuterated form of linoleic polyunsaturated fatty acid (D4-Lnn) completely inhibits necrosis and greatly reduces apoptotic cell death with an increase in the concentration of fatty acid in the medium. It was shown for the first time that D4-Lnn, through the activation of the phosphoinositide calcium system of astrocytes, causes their reactivation, which correlates with the general cytoprotective effect on the cortical neurons and astrocytes in vitro. The mechanism of the cytoprotective action of D4-Lnn involves the inhibition of the OGD-induced calcium ions, increase in the cytosolic and reactive oxygen species (ROS) overproduction, the enhancement of the expression of protective genes, and the suppression of damaging proteins.https://www.mdpi.com/1422-0067/22/24/13216oxygen-glucose deprivationcell deathcortexastrocytecell protectionsignaling
spellingShingle Egor A. Turovsky
Elena G. Varlamova
Sergey V. Gudkov
Egor Y. Plotnikov
The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
International Journal of Molecular Sciences
oxygen-glucose deprivation
cell death
cortex
astrocyte
cell protection
signaling
title The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
title_full The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
title_fullStr The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
title_full_unstemmed The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
title_short The Protective Mechanism of Deuterated Linoleic Acid Involves the Activation of the Ca<sup>2+</sup> Signaling System of Astrocytes in Ischemia In Vitro
title_sort protective mechanism of deuterated linoleic acid involves the activation of the ca sup 2 sup signaling system of astrocytes in ischemia in vitro
topic oxygen-glucose deprivation
cell death
cortex
astrocyte
cell protection
signaling
url https://www.mdpi.com/1422-0067/22/24/13216
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