Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity
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- 作者：Cora S Thiel (1) (2)
Katrin Paulsen (1)
Gesine Bradacs (1) (3)
Karolin Lust (3) (4)
Svantje Tauber (1)
Claudia Dumrese (1) (5)
Andre Hilliger (6)
Kathrin Schoppmann (1) (3)
Josefine Biskup (1)
Nadine G?lz (1)
Chen Sang (7)
Urs Ziegler (5)
Karl-Heinrich Grote (3)
Frauke Zipp (8)
Fengyuan Zhuang (7)
Frank Engelmann (6) (9)
Ruth Hemmersbach (10)
Augusto Cogoli (11)
Oliver Ullrich (1) (12) (3) - 关键词：Adaptive immunity ; spaceflight ; signal transduction ; gravisensitivity
- 刊名：Cell Communication and Signaling
- 出版年：2012
- 出版时间：December 2012
- 年：2012
- 卷：10
- 期：1
- 全文大小：573KB
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Katrin Paulsen (1)
Gesine Bradacs (1) (3)
Karolin Lust (3) (4)
Svantje Tauber (1)
Claudia Dumrese (1) (5)
Andre Hilliger (6)
Kathrin Schoppmann (1) (3)
Josefine Biskup (1)
Nadine G?lz (1)
Chen Sang (7)
Urs Ziegler (5)
Karl-Heinrich Grote (3)
Frauke Zipp (8)
Fengyuan Zhuang (7)
Frank Engelmann (6) (9)
Ruth Hemmersbach (10)
Augusto Cogoli (11)
Oliver Ullrich (1) (12) (3)
1. Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
2. Institute of Medical Physics and Biophysics, University of Muenster, Heisenbergstrasse 11, 48149, Muenster, Germany
3. Department of Machine Design, Engineering Design and Product Development, Institute of Mechanical Engineering, Otto-von-Guericke-University Magdeburg, Universitaetsplatz 2, 39106, Magdeburg, Germany
4. Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany
5. Center for Microsocopy and Image Analysis, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland
6. KEK GmbH, Kemberger Str. 5, 06905, Bad Schmiedeberg, Germany
7. School of Biological Science and Medical Engineering, Beihang University, 37 Xueyuan Rd., Beijing, 100191, China
8. Clinic for Neurology, University Medical Center of Johannes Gutenberg-University Mainz, Langenbeckstra?e 1, 55131, Mainz, Germany
9. University of Applied Science Jena, Carl-Zeiss-Promenade 2, 07745, Jena, Germany
10. Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany
11. Zero-G Life Tec, Riedhofstrasse 273, 8049, Zurich, Switzerland
12. Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Kragujevac, Switzerland
文摘
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 Waf1/Cip1 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+ 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.