• Medientyp: E-Artikel
  • Titel: Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity
  • Beteiligte: 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
  • Erschienen: Springer Science and Business Media LLC, 2012
  • Erschienen in: Cell Communication and Signaling, 10 (2012) 1
  • Sprache: Englisch
  • DOI: 10.1186/1478-811x-10-1
  • ISSN: 1478-811X
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractIn 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 p21Waf1/Cip1protein 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.
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