Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier
Ionizing radiation (IR) causes disturbances in the functions of the gastrointestinal tract. Given the therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against IR-induced disturbances in the barrier and transport properties of the jejunum and co...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/278 |
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| author | Alexander G. Markov Alexandra A. Livanova Arina A. Fedorova Violetta V. Kravtsova Igor I. Krivoi |
| author_facet | Alexander G. Markov Alexandra A. Livanova Arina A. Fedorova Violetta V. Kravtsova Igor I. Krivoi |
| author_sort | Alexander G. Markov |
| collection | DOAJ |
| description | Ionizing radiation (IR) causes disturbances in the functions of the gastrointestinal tract. Given the therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against IR-induced disturbances in the barrier and transport properties of the jejunum and colon of rats. Male Wistar rats were subjected to 6-day intraperitoneal injections of vehicle or ouabain (1 µg/kg/day). On the fourth day of injections, rats were exposed to total-body X-ray irradiation (10 Gy) or a sham irradiation. Isolated tissues were examined 72 h post-irradiation. Electrophysiological characteristics and paracellular permeability for sodium fluorescein were measured in an Ussing chamber. Histological analysis and Western blotting were also performed. In the jejunum tissue, ouabain exposure did not prevent disturbances in transepithelial resistance, paracellular permeability, histological characteristics, as well as changes in the expression of claudin-1, -3, -4, tricellulin, and caspase-3 induced by IR. However, ouabain prevented overexpression of occludin and the pore-forming claudin-2. In the colon tissue, ouabain prevented electrophysiological disturbances and claudin-2 overexpression. These observations may reveal a mechanism by which circulating ouabain maintains tight junction integrity under IR-induced intestinal dysfunction. |
| first_indexed | 2024-03-08T15:05:05Z |
| format | Article |
| id | doaj.art-25e4c6d7f6fe43f785518ce5621d75cc |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:05Z |
| publishDate | 2023-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-25e4c6d7f6fe43f785518ce5621d75cc2024-01-10T14:58:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125127810.3390/ijms25010278Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue BarrierAlexander G. Markov0Alexandra A. Livanova1Arina A. Fedorova2Violetta V. Kravtsova3Igor I. Krivoi4Department of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaDepartment of General Physiology, St. Petersburg State University, 199034 St. Petersburg, RussiaIonizing radiation (IR) causes disturbances in the functions of the gastrointestinal tract. Given the therapeutic potential of ouabain, a specific ligand of the Na,K-ATPase, we tested its ability to protect against IR-induced disturbances in the barrier and transport properties of the jejunum and colon of rats. Male Wistar rats were subjected to 6-day intraperitoneal injections of vehicle or ouabain (1 µg/kg/day). On the fourth day of injections, rats were exposed to total-body X-ray irradiation (10 Gy) or a sham irradiation. Isolated tissues were examined 72 h post-irradiation. Electrophysiological characteristics and paracellular permeability for sodium fluorescein were measured in an Ussing chamber. Histological analysis and Western blotting were also performed. In the jejunum tissue, ouabain exposure did not prevent disturbances in transepithelial resistance, paracellular permeability, histological characteristics, as well as changes in the expression of claudin-1, -3, -4, tricellulin, and caspase-3 induced by IR. However, ouabain prevented overexpression of occludin and the pore-forming claudin-2. In the colon tissue, ouabain prevented electrophysiological disturbances and claudin-2 overexpression. These observations may reveal a mechanism by which circulating ouabain maintains tight junction integrity under IR-induced intestinal dysfunction.https://www.mdpi.com/1422-0067/25/1/278ionizing radiationouabainepitheliumtight junctionsclaudinsgastrointestinal acute radiation syndrome |
| spellingShingle | Alexander G. Markov Alexandra A. Livanova Arina A. Fedorova Violetta V. Kravtsova Igor I. Krivoi Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier International Journal of Molecular Sciences ionizing radiation ouabain epithelium tight junctions claudins gastrointestinal acute radiation syndrome |
| title | Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier |
| title_full | Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier |
| title_fullStr | Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier |
| title_full_unstemmed | Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier |
| title_short | Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier |
| title_sort | chronic ouabain targets pore forming claudin 2 and ameliorates radiation induced damage to the rat intestinal tissue barrier |
| topic | ionizing radiation ouabain epithelium tight junctions claudins gastrointestinal acute radiation syndrome |
| url | https://www.mdpi.com/1422-0067/25/1/278 |
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