The kinetics of translocation and cellular quantity of protein kinase C in human leukocytes are modified during spaceflight

Hatton, Jason; Gaubert, F.; Lewis, Marian L.; Darsel, Yann; Ohlmann, Philippe; Cazenave, Jean‐Pierre; Schmitt, Didier

doi:10.1096/fasebj.13.9001.s23

Cited by 56 publications

(44 citation statements)

References 28 publications

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“…It is noteworthy that experiments performed on U937 cells cultured in the RWV or in the RPM yielded results which are very similar to those obtained in space [Hatton et al, 1999;Maier, 2006], suggesting that these bioreactors are reliable systems to study cell proliferation and cytokine synthesis in reduced gravity. Similar conclusions were reached for studies on immune cells [Ritz et al, 2006].…”

supporting

confidence: 61%

Gravitational unloading induces an anti‐angiogenic phenotype in human microvascular endothelial cells

Mariotti

Maier

2007

J of Cellular Biochemistry

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Creating conditions similar to those occurring during exposure of cells to microgravity modulates endothelial functions. We have previously demonstrated that human macrovascular endothelial cells in simulated hypogravity proliferate faster than controls, partly because they downregulate interleukin 1alpha. On the contrary, murine microvascular endothelial cells are growth inhibited in simulated hypogravity, and this is due, at least in part, to the decrease of interleukin 6. Since endothelial cells are very heterogeneous and differences between various species have been reported, we exposed human microvascular cells to gravitational unloading and found that it retards cell growth without affecting cell migration. Interestingly, we detected the induction of Tissue Inhibitor of Metalloprotease-2, which inhibits endothelial growth in vitro and angiogenesis in vivo. Together with the finding that hypogravity stimulates the synthesis of nitric oxide, involved also in neovascularization, our results underscore a modulation of the angiogenic properties of microvascular human endothelial cells. We also show that hypogravity inhibits proteasome activity, thus suggesting that post-translational mechanisms are involved in the adaptations of these cells to hypogravity. These results underscore that hypogravity differently impacts on micro- and macro-vascular human endothelial cells. In particular, these results may shed some light on the molecular mechanisms contributing to the impairment of angiogenesis observed in different models in space. Our data might also explain why bioengineered tissues to be used for regenerative medicine fail to neovascularize when assembled in simulated hypogravity.

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supporting

confidence: 61%

Gravitational unloading induces an anti‐angiogenic phenotype in human microvascular endothelial cells

Mariotti

Maier

2007

J of Cellular Biochemistry

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“…Results of studies in both simulated and true microgravity show decreases of the proliferation and function of leukocytes. In particular, the growth of U937 cells flown to space was significantly lower than ground controls (14), and this could be due, in part, to the modification of the kinetics and the quantity of translocation of protein kinase C, thus suggesting an effect of microgravity on early cell activation events (14,18). Accordingly, by using the RWV as a device to simulate microgravity, U937 cells proliferate more slowly than controls.…”

Section: Discussionmentioning

confidence: 97%

Impact of Simulated Microgravity on Cell Cycle Control and Cytokine Release by U937 Cells

Maier

2006

Int J Immunopathol Pharmacol

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Previous experiments from flight- and ground-based model systems indicate unexpected alterations of human leukocytes, leading to growth retardation and depression of mitogenic activation. The response of myelomonocytic U937 cells to simulated microgravity was therefore investigated. To this purpose, U937 cells were cultured in the NASA-developed bioreactor Rotating Wall Vessel (RWV) as a device to simulate microgravity on earth. No apoptosis was detected, in part because of the up-regulation of hsp70. In agreement with results obtained in space-flown U937 cells, the cells grew more slowly in the RWV than under normal conditions and this correlated with the down-modulation of cdc25B. Marked alterations of the cytokine secretion profile and, in particular, of inflammatory chemokines, as well as a decrease of the proteasome activity, were also observed in response to microgravity.

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“…In low gravity, monocytes lost their capability of secreting IL-1 [Cogoli, 1993] and expressing IL-2 receptor [Hashemi et al, 1999]. Space flight experiments revealed that the distribution, cellular quantity and kinetics of translocation of PKC -a key protein controlling growth and differentiation of monocytes into macrophages -are altered in U937 monocytes in low gravity [Schmitt et al, 1996;Hatton et al, 1999Hatton et al, , 2002. Recently, the examination of gene expression of monocytes under low gravity demonstrated significant changes in gene induction associated with differentiation of monocytes into macrophages [Hughes-Fulford et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

Space flight affects motility and cytoskeletal structures in human monocyte cell line J‐111

et al. 2011

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Certain functions of immune cells in returning astronauts are known to be altered. A dramatic depression of the mitogenic in vitro activation of human lymphocytes was observed in low gravity. T-cell activation requires the interaction of different type of immune cells as T-lymphocytes and monocytes. Cell motility based on a continuous rearrangement of the cytoskeletal network within the cell is essential for cell-cell contacts. In this investigation on the International Space Station we studied the influence of low gravity on different cytoskeletal structures in adherent monocytes and their ability to migrate. J-111 monocytes were incubated on a colloid gold substrate attached to a cover slide. Migrating cells removed the colloid gold, leaving a track recording cell motility. A severe reduction of the motility of J-111 cells was found in low gravity compared to 1g in-flight and ground controls. Cell shape appeared more contracted, whereas the control cells showed the typical morphology of migrating monocytes, i.e., elongated and with pseudopodia. A qualitative and quantitative analysis of the structures of F-actin, β-tubulin and vinculin revealed that exposure of J-111 cells to low gravity affected the distribution of the different filaments and significantly reduced the fluorescence intensity of F-actin fibers. Cell motility relies on an intact structure of different cytoskeletal elements. The highly reduced motility of monocytes in low gravity must be attributed to the observed severe disruption of the cytoskeletal structures and may be one of the reasons for the dramatic depression of the in vitro activation of human lymphocytes.

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The kinetics of translocation and cellular quantity of protein kinase C in human leukocytes are modified during spaceflight

Cited by 56 publications

References 28 publications

Gravitational unloading induces an anti‐angiogenic phenotype in human microvascular endothelial cells

Gravitational unloading induces an anti‐angiogenic phenotype in human microvascular endothelial cells

Impact of Simulated Microgravity on Cell Cycle Control and Cytokine Release by U937 Cells

Space flight affects motility and cytoskeletal structures in human monocyte cell line J‐111

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