Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity
Autor: | Svantje Tauber, Gesine Bradacs, Nadine Gölz, Urs Ziegler, Frauke Zipp, Kathrin Schoppmann, Josephine Biskup, Oliver Ullrich, Augusto Cogoli, Cora S. Thiel, Frank Engelmann, Ruth Hemmersbach, Karoline Lust, Karl-Heinrich Grote, Andre Hilliger, Katrin Paulsen, Claudia Dumrese, Fengyuan Zhuang, Chen Sang |
---|---|
Přispěvatelé: | University of Zurich |
Jazyk: | angličtina |
Rok vydání: | 2012 |
Předmět: |
10017 Institute of Anatomy
CD3 Adaptive immunity lcsh:Medicine 610 Medicine & health Biology Biochemistry Jurkat cells spaceflight Immune system gravisensitivity lcsh:QH573-671 Molecular Biology lcsh:Cytology Research lcsh:R CD28 Cell Biology Cell cycle Acquired immune system Cell biology 10076 Center for Integrative Human Physiology biology.protein 570 Life sciences biology Histone deacetylase Signal transduction 10024 Center for Microscopy and Image Analysis signal transduction |
Zdroj: | Cell Communication and Signaling, Vol 10, Iss 1, p 1 (2012) Cell Communication and Signaling : CCS |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |