Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

• Published in: Cell communication and signaling 2012-01, Vol.10 (1), p.1-1, Article 1
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Aerospace engineering; Anatomy & physiology; Biomedical research; Cell cycle; Earth; Experiments; gravisensitivity; Gravity; Kinases; Lymphocytes; Messenger RNA; Physiological aspects; Product development; signal transduction; spaceflight; Studies; T cells
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/1478-811X-10-1

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.