Gravity alteration (micro- and hypergravity) is known to influence cell functions. Space experiments with different cell systems have shown altered gene expression and signal transduction, chromosomal abnormalities as well as changes in energy metabolism, cell proliferation, and the cytoskeleton. We are especially interested in the regulation of signaling activities in normal and transformed cells under altered gravity conditions, e.g. how normal and transformed human melanocytes respond to changed environmental factors. These studies are essential with respect to the minimization of the cancer risk for astronauts during long-term spaceflight.
For human melanocytes, it has been shown that signaling via the second messenger cyclic guanosine 3’:5’-monophosphate (cGMP) plays an important role in melanocyte biology, e.g., the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP pathway is involved in UVB-induced melanogenesis and melanocyte-extracellular matrix component interactions, which may contribute to loss of melanocytes or melanoma metastasis. In addition, we found that different guanylyl cyclase isoforms are responsible for cGMP synthesis in melanocytic cells. Furthermore, we could demonstrate that the cGMP turnover is altered under variable gravity conditions (hypergravity): normal melanocytes and nonmetastatic, but not highly metastatic cells responded with an increase in cGMP efflux under conditions of reduced cGMP hydrolysis or accelerated cGMP synthesis, which was related to an enhanced expression of the multidrug resistance proteins 4/5 as selective cGMP exporters as shown on mRNA and protein levels using real-time polymerase chain reaction and flow cytometric analysis.
Thus, cGMP appears to be important in the adaptation process of human melanocytes to gravitational stress and important for malignant transformation. The scientific goal is therefore to investigate the role of NO and cGMP-modulated gene expression which is involved in (patho)physiological processes such as the regulation of melanocyte and melanoma cell proliferation and apoptosis, melanogenesis, cell-cell and cell-extracellular matrix interactions, or metastasis under the conditions of simulated and/or real microgravity (s. Space simulation facilities) with or without an irradiation.
Dr. Krassimira Ivanova++49 2203 601 3074Email: Krassimira Ivanova
Prof. Dr. Rupert Gerzer (RWTH Aachen)++49 2203 601 3115Email: Rupert Gerzer
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