Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels
To date, there are practically no data on the mechanisms of the selenium nanoparticles action on calcium homeostasis, intracellular signaling in cancer cells, and on the relationship of signaling pathways activated by an increase in Ca<sup>2+</sup> in the cytosol with the induction of ap...
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MDPI AG
2021-08-01
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| author | Egor A. Turovsky Elena G. Varlamova |
| author_facet | Egor A. Turovsky Elena G. Varlamova |
| author_sort | Egor A. Turovsky |
| collection | DOAJ |
| description | To date, there are practically no data on the mechanisms of the selenium nanoparticles action on calcium homeostasis, intracellular signaling in cancer cells, and on the relationship of signaling pathways activated by an increase in Ca<sup>2+</sup> in the cytosol with the induction of apoptosis, which is of great importance. The study of these mechanisms is important for understanding the cytotoxic effect of selenium nanoparticles and the role of this microelement in the regulation of carcinogenesis. The work is devoted to the study of the role of selenium nanoparticles obtained by laser ablation in the activation of the calcium signaling system and the induction of apoptosis in human glioblastoma cells (A-172 cell line). In this work, it was shown for the first time that the generation of Ca<sup>2+</sup> signals in A-172 cells occurs in response to the application of various concentrations of selenium nanoparticles. The intracellular mechanism responsible for the generation of these Ca<sup>2+</sup> signals has also been established. It was found that nanoparticles promote the mobilization of Ca<sup>2+</sup> ions from the endoplasmic reticulum through the IP<sub>3</sub>-receptor. This leads to the activation of vesicular release of ATP through connexin hemichannels (Cx43) and paracrine cell activation through purinergic receptors (mainly P2Y). In addition, it was shown that the activation of this signaling pathway is accompanied by an increase in the expression of pro-apoptotic genes and the induction of apoptosis. For the first time, the role of Cx43 in the regulation of apoptosis caused by selenium nanoparticles in glioblastoma cells has been shown. It was found that inhibition of Cx43 leads to a significant suppression of the induction of apoptosis in these cells after 24 h treatment of cells with selenium nanoparticles at a concentration of 5 µg/mL. |
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| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T09:00:14Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-44546908fbb14240b0d31db45feefd432023-11-22T06:49:53ZengMDPI AGBiology2079-77372021-08-0110874310.3390/biology10080743Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 HemichannelsEgor A. Turovsky0Elena G. Varlamova1Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Scienes”, 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 Scienes”, Institute of Cell Biophysics of the Russian Academy of Sciences, 142290 Pushchino, RussiaTo date, there are practically no data on the mechanisms of the selenium nanoparticles action on calcium homeostasis, intracellular signaling in cancer cells, and on the relationship of signaling pathways activated by an increase in Ca<sup>2+</sup> in the cytosol with the induction of apoptosis, which is of great importance. The study of these mechanisms is important for understanding the cytotoxic effect of selenium nanoparticles and the role of this microelement in the regulation of carcinogenesis. The work is devoted to the study of the role of selenium nanoparticles obtained by laser ablation in the activation of the calcium signaling system and the induction of apoptosis in human glioblastoma cells (A-172 cell line). In this work, it was shown for the first time that the generation of Ca<sup>2+</sup> signals in A-172 cells occurs in response to the application of various concentrations of selenium nanoparticles. The intracellular mechanism responsible for the generation of these Ca<sup>2+</sup> signals has also been established. It was found that nanoparticles promote the mobilization of Ca<sup>2+</sup> ions from the endoplasmic reticulum through the IP<sub>3</sub>-receptor. This leads to the activation of vesicular release of ATP through connexin hemichannels (Cx43) and paracrine cell activation through purinergic receptors (mainly P2Y). In addition, it was shown that the activation of this signaling pathway is accompanied by an increase in the expression of pro-apoptotic genes and the induction of apoptosis. For the first time, the role of Cx43 in the regulation of apoptosis caused by selenium nanoparticles in glioblastoma cells has been shown. It was found that inhibition of Cx43 leads to a significant suppression of the induction of apoptosis in these cells after 24 h treatment of cells with selenium nanoparticles at a concentration of 5 µg/mL.https://www.mdpi.com/2079-7737/10/8/743selenium nanoparticlescancerapoptosiscalcium signalingconnexinspurinoreceptors |
| spellingShingle | Egor A. Turovsky Elena G. Varlamova Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels Biology selenium nanoparticles cancer apoptosis calcium signaling connexins purinoreceptors |
| title | Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels |
| title_full | Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels |
| title_fullStr | Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels |
| title_full_unstemmed | Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels |
| title_short | Mechanism of Ca<sup>2+</sup>-Dependent Pro-Apoptotic Action of Selenium Nanoparticles, Mediated by Activation of Cx43 Hemichannels |
| title_sort | mechanism of ca sup 2 sup dependent pro apoptotic action of selenium nanoparticles mediated by activation of cx43 hemichannels |
| topic | selenium nanoparticles cancer apoptosis calcium signaling connexins purinoreceptors |
| url | https://www.mdpi.com/2079-7737/10/8/743 |
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