Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity
<p>Abstract</p> <p>In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness&quo...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-01-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://www.biosignaling.com/content/10/1/1 |
| _version_ | 1811329388199804928 |
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| author | Thiel Cora S Paulsen Katrin Bradacs Gesine Lust Karolin Tauber Svantje Dumrese Claudia Hilliger Andre Schoppmann Kathrin Biskup Josefine Gölz Nadine Sang Chen Ziegler Urs Grote Karl-Heinrich Zipp Frauke Zhuang Fengyuan Engelmann Frank Hemmersbach Ruth Cogoli Augusto Ullrich Oliver |
| author_facet | Thiel Cora S Paulsen Katrin Bradacs Gesine Lust Karolin Tauber Svantje Dumrese Claudia Hilliger Andre Schoppmann Kathrin Biskup Josefine Gölz Nadine Sang Chen Ziegler Urs Grote Karl-Heinrich Zipp Frauke Zhuang Fengyuan Engelmann Frank Hemmersbach Ruth Cogoli Augusto Ullrich Oliver |
| author_sort | Thiel Cora S |
| collection | DOAJ |
| description | <p>Abstract</p> <p>In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 <sup>Waf1/Cip1 </sup>protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4<sup>+ </sup>T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT) inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC) inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space.</p> |
| first_indexed | 2024-04-13T15:43:00Z |
| format | Article |
| id | doaj.art-5947e4232f074b63a0a5e907f4fa781b |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-13T15:43:00Z |
| publishDate | 2012-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-5947e4232f074b63a0a5e907f4fa781b2022-12-22T02:41:05ZengBMCCell Communication and Signaling1478-811X2012-01-01101110.1186/1478-811X-10-1Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravityThiel Cora SPaulsen KatrinBradacs GesineLust KarolinTauber SvantjeDumrese ClaudiaHilliger AndreSchoppmann KathrinBiskup JosefineGölz NadineSang ChenZiegler UrsGrote Karl-HeinrichZipp FraukeZhuang FengyuanEngelmann FrankHemmersbach RuthCogoli AugustoUllrich Oliver<p>Abstract</p> <p>In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 <sup>Waf1/Cip1 </sup>protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4<sup>+ </sup>T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT) inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC) inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space.</p>http://www.biosignaling.com/content/10/1/1Adaptive immunityspaceflightsignal transductiongravisensitivity |
| spellingShingle | Thiel Cora S Paulsen Katrin Bradacs Gesine Lust Karolin Tauber Svantje Dumrese Claudia Hilliger Andre Schoppmann Kathrin Biskup Josefine Gölz Nadine Sang Chen Ziegler Urs Grote Karl-Heinrich Zipp Frauke Zhuang Fengyuan Engelmann Frank Hemmersbach Ruth Cogoli Augusto Ullrich Oliver Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity Cell Communication and Signaling Adaptive immunity spaceflight signal transduction gravisensitivity |
| title | Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity |
| title_full | Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity |
| title_fullStr | Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity |
| title_full_unstemmed | Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity |
| title_short | Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity |
| title_sort | rapid alterations of cell cycle control proteins in human t lymphocytes in microgravity |
| topic | Adaptive immunity spaceflight signal transduction gravisensitivity |
| url | http://www.biosignaling.com/content/10/1/1 |
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