Dichotomal effect of space flight-associated microgravity on stress-activated protein kinases in innate immunity

Gravitational forces can impose physical stresses on the human body as it functions to maintain homeostasis. It has been reported that astronauts exposed to microgravity experience altered biological functions and many subsequent studies on the effects of microgravity have therefore been conducted. However, the anticancer mechanisms of simulated microgravity remain unclear. We previously showed that the proliferation of human Hodgkin’s lymphoma (HL) cells was inhibited when these cells were cultured in time-averaged simulated microgravity (taSMG). In the present study, we investigated whether taSMG produced an anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their reactive oxygen species (ROS) production and NADPH oxidase family gene expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP levels were decreased. Furthermore, human HL cells exposed to taSMG underwent autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an innovative therapeutic approach to HL that is markedly different from conventional chemotherapy and radiotherapy.

Section: Discussionmentioning

confidence: 99%

Microgravity induces autophagy via mitochondrial dysfunction in human Hodgkin’s lymphoma cells

Jeong

Kim

Lim

et al. 2018

“…This analysis showed the presence of several signatures of autoimmune repression ( Table 1 ), which were never reported. A recent study speculated microgravity could be a measure for fighting autoimmune disease 9 . Further, tissue engineering model in microgravity showed the enhanced survival, better secretory profile and better insulin normalization of beta islet cells compare to ground control 42 .…”

Section: Discussionmentioning

confidence: 99%

“…During today’s space missions, a short to moderate microgravity exposure (days to months) induces several physiological changes in human body including bone and muscle loss, puffiness in the face, change in cardiovascular physiology, catecholamine cardiomyopathy, insufficient blood flow in the brain, genitourinary issues and disturbance in neurovestibular system 2 3 4 5 6 7 . Further, microgravity induces deregulation of human immune systems 8 9 . Multiple gene expression studies showed microgravity-induced signature of early inhibition in T cell activation 10 , impaired endothelial cell function 11 , cellular senescence 12 , alteration of genes related to cell cycle 13 14 , cell adhesion 11 , oxidative phosphorylation 14 and apoptosis 14 .…”

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confidence: 99%

“…Multiple gene expression studies showed microgravity-induced signature of early inhibition in T cell activation 10 , impaired endothelial cell function 11 , cellular senescence 12 , alteration of genes related to cell cycle 13 14 , cell adhesion 11 , oxidative phosphorylation 14 and apoptosis 14 . It has been showed that the reduced immunity may result from inhibition of NF- κB/Rel pathway, downregulation of early T cell activation genes, IFN- ϒ and EL-2Rα genes 15 and impairment of Jun-N-terminal kinase activity 9 . The compromised immune system increases the risk of infection by pathogen like salmonella, virulence of which is increased in microgravity 16 .…”

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confidence: 99%

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A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

Mukhopadhyay

Saha

Palanisamy

et al. 2016

Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

“…This ultra-low range and sensitive space accelerometer will undergo a series of ground-based pre-flight experiments to verify its function and performance. Currently, various facilities are available to perform microgravity experiments near the ground, such as drop towers or drop wells, parabolic flights, balloon-drops and sounding rockets 7 8 9 . The small residual gravity, low cost and high throughput of experiments 10 make the drop tower become an ideal choice for our ground-based test.…”

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confidence: 99%

Microgravity Level Measurement of the Beijing Drop Tower Using a Sensitive Accelerometer

Liu

Sun

et al. 2016

Drop tower is the most common ground-based facility to provide microgravity environment and widely used in many science experiments. A differential space accelerometer has been proposed to test the spin-gravity interaction between rotating extended bodies onboard a drag-free satellite. In order to assist design and test of this inertial sensor in a series of ground- based pre-flight experiments, it is very important to know accurately the residual acceleration of drop towers. In this report, a sensitive instrument for this purpose was built with a high-performance servo quartz accelerometer, and the dedicated interface electronics design providing small full-scale range and high sensitivity, up to 136.8 V/g0. The residual acceleration at the Beijing drop tower was measured using two different drop capsules. The experimental result shows that the microgravity level of the free-falling double capsule is better than 2 × 10−4g0 (Earth’s gravity). The measured data in this report provides critical microgravity information for design of the following ground experiments.