Research
Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity
- † Equal contributors
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, Langenbeckstraße 1, 55131 Mainz, Germany
9 University of Applied Science Jena, Carl-Zeiss-Promenade 2, 07745 Jena, Germany
10 German Aerospace Center (DLR), Institute of Aerospace Medicine, 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, Switzerland
Cell Communication and Signaling 2012, 10:1 doi:10.1186/1478-811X-10-1
Published: 24 January 2012Abstract
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.
