The Effects of Weightlessness on the Human Organism and Mammalian Cells

Extracellular matrix proteins, adhesion molecules, and cytoskeletal proteins form a dynamic network interacting with signalling molecules as an adaptive response to altered gravity. An important issue is the exact differentiation between real microgravity responses of the cells or cellular reactions to hypergravity and/or vibrations. To determine the effects of real microgravity on human cells, we used four DLR parabolic flight campaigns and focused on the effects of short-term microgravity (22 s), hypergravity (1.8 g), and vibrations on ML-1 thyroid cancer cells. No signs of apoptosis or necrosis were detectable. Gene array analysis revealed 2430 significantly changed transcripts. After 22 s microgravity, the F-actin and cytokeratin cytoskeleton was altered, and ACTB and KRT80 mRNAs were significantly upregulated after the first and thirty-first parabolas. The COL4A5 mRNA was downregulated under microgravity, whereas OPN and FN were significantly upregulated. Hypergravity and vibrations did not change ACTB, KRT-80 or COL4A5 mRNA. MTSS1 and LIMA1 mRNAs were downregulated/slightly upregulated under microgravity, upregulated in hypergravity and unchanged by vibrations. These data indicate that the graviresponse of ML-1 cells occurred very early, within the first few seconds. Downregulated MTSS1 and upregulated LIMA1 may be an adaptive mechanism of human cells for stabilizing the cytoskeleton under microgravity conditions.

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“…Changes of the cytoskeleton were also reported by several other authors [55,56]. This process starts very early on.…”

Section: Short-term Microgravity Alters Gene Expression Of Extracellusupporting

confidence: 79%

Differential Gene Regulation under Altered Gravity Conditions in Follicular Thyroid Cancer Cells: Relationship between the Extracellular Matrix and the Cytoskeleton

Ulbrich

Pietsch

Grosse

et al. 2011

Cell Physiol Biochem

121

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“…During and after spaceflights, astronauts suffer from many different health problems, including an impaired immune system, bone and muscle loss, orthostatic intolerance, and cardiovascular problems [14,15]. The latter are very likely caused by an endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Altered Gravity and Vibration on Endothelial Cells During a Parabolic Flight

Wehland

Ma²,

Braun³

et al. 2013

Cell Physiol Biochem

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Background: Endothelial cells (EC) cultured under altered gravity conditions show a cytoskeletal disorganization and differential gene expression (short-term effects), as well as apoptosis in adherently growing EC or formation of tubular 3D structures (long-term effects). Methods: Investigating short-term effects of real microgravity, we exposed EC to parabolic flight maneuvers and analysed them on both protein and transcriptional level. The effects of hypergravity and vibration were studied separately. Results: Pan-actin and tubulin proteins were elevated by vibration and down-regulated by hypergravity. β-Actin was reduced by vibration. Moesin protein was reduced by both vibration and hypergravity, ezrin potein was strongly elevated under vibration. Gene expression of ACTB, CCND1, CDC6, CDKN1A, VEGFA, FLK-1, EZR, ITBG1, OPN, CASP3, CASP8, ANXA2, and BIRC5 was reduced under vibration. With the exception of CCNA2, CCND1, MSN, RDX, OPN, BIRC5, and ACTB all investigated genes were downregulated by hypergravity. After one parabola (P) CCNA2, CCND1, CDC6, CDKN1A, EZR, MSN, OPN, VEGFA, CASP3, CASP8, ANXA1, ANXA2, and BIRC5 were up-, while FLK1 was downregulated. EZR, MSN, OPN, ANXA2, and BIRC5 were upregulated after 31P. Conclusions: Genes of the cytoskeleton, angiogenesis, extracellular matrix, apoptosis, and cell cycle regulation were affected by parabolic flight maneuvers. We show that the microgravity stimulus is stronger than hypergravity/vibration.

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“…Exposure to space flights is associated with several stress factors such as microgravity and circadian alteration. These conditions can affect the physiological function of human and animal organism (1,2). These include cardiovascular, muscle and immune related problems, decreased bone mineral density, and circadian rhythm-related problems involving sleep and performance (3).…”

Section: Introductionmentioning

confidence: 99%