Extensive research with purely natural killer cells in simulated weightlessness and in authentic microgravity on board the ISS uncovered that neither cytotoxic results nor interferon production is altered in microgravity, In our examine we uncovered that p21Waf1 Cip1 mRNA expression is enhanced in microgravity in contrast to one g in CD3 CD28 activated Jurkat T cells and in main CD4 T cells, but also in non stimulated Jurkat T cells. p21Waf1 Cip1 is probably the p53 target molecules, inhibiting the exercise in the cyclinB1 Cdc2 complicated, resulting in a cell cycle arrest. The cell cycle arrest can be induced experimentally by stimulating cells with PMA, PMA activates the protein kinase C, which prospects to a p21Waf1 Cip1 upregulation, a lower of cyclinB1 cdc2 concentration and subsequent inhibition with the cell cycle on the G1 S and G2 M phase.
We even more identified that the histone acetyl transferase inhibitor curcumin abrogated the microgravity induced overexpression of p21Waf1 Cip1 mRNA, whereas the histone deacetylase inhibitor valproic acid enhanced p21Waf1 Cip1 mRNA expression in micrograv ity. Interestingly, a recent research found epigenetic altera tions in cells exposed to simulated weightlessness and also selelck kinase inhibitor exposed a decreased expression of the histone deace tylase, Other scientific studies in long lasting simulated bodyweight lessness found intact T cell receptor signalling, but alterations in cell cycle manage and upregulation of p21Waf1 Cip1, The p21 Waf cip1 gene consists of 492 bp coding sequence emerging from a pre mRNA of maximally 8682 bp, compact adequate to perform being a regu lator for cellular responses through differential gene expres sion. In human fibroblasts p21 Waf cip1 expression ranges have been greater 8 9 fold only immediately after 30 min of microbeam irradiation, Here we demonstrate that gene expression amounts are altered even within tens of seconds.
The observed overexpression of p21Waf cip1 is conceivable by speedy transcriptional induction considering the large elongation speed in the RNA polymerase II. Though mea sured elongation velocities reached up to four. over at this website three kb per min, theoretically velocities even over 50 kb per min ute are already calculated allowing a substantial maximize in gene expression after 20s only. The p21 gene is underneath the transcriptional control of p53, suggesting that p21 may possibly encourage p53 dependent cell cycle arrest or apoptosis, We a short while ago found that p53 was phosphorylated rapidly in proliferating human U937 cells throughout the microgravity phase of parabolic flights, For that reason, a role of p53 in micro gravity dependent p21 expression can be assumed. On the other hand, the quick look of p21 RNA in the course of 20 seconds of microgravity suggests a additional direct result of altered gravity on p21 transcriptional regulation.