How and why does the proteome respond to microgravity?

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.

show abstract

“…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: 77%

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

Self Cite

121

View full text Add to dashboard Cite

show abstract

“…The downregulation of these signaling pathways may lead to an alteration of the cell cycle (33). In addition to its major role in the cell response to radiation (34,35), the regulation of the cell cycle has been shown to be affected by simulated microgravity (36). GSEA revealed that gene sets involved in the positive regulation of the cell cycle were downregulated in all treatments.…”

Section: The Rpm Has a Dominant Impact On Single Gene Expressionmentioning

confidence: 99%

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck

Moreels

Quintens

et al. 2014

International Journal of Molecular Medicine

Self Cite

View full text Add to dashboard Cite

Abstract. microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high-linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

show abstract

“…[1][2][3][4][5][6][7] For a long time, it has been clear that microgravity induces alterations in human cells. [8][9][10] However, the corresponding mechanisms are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

Grimm

Wehland

Pietsch

et al. 2014

Tissue Engineering Part B: Reviews

Self Cite

124

137

View full text Add to dashboard Cite

Tissue engineering in simulated (s-) and real microgravity (r-mg) is currently a topic in Space medicine contributing to biomedical sciences and their applications on Earth. The principal aim of this review is to highlight the advances and accomplishments in the field of tissue engineering that could be achieved by culturing cells in Space or by devices created to simulate microgravity on Earth. Understanding the biology of three-dimensional (3D) multicellular structures is very important for a more complete appreciation of in vivo tissue function and advancing in vitro tissue engineering efforts. Various cells exposed to r-mg in Space or to s-mg created by a random positioning machine, a 2D-clinostat, or a rotating wall vessel bioreactor grew in the form of 3D tissues. Hence, these methods represent a new strategy for tissue engineering of a variety of tissues, such as regenerated cartilage, artificial vessel constructs, and other organ tissues as well as multicellular cancer spheroids. These aggregates are used to study molecular mechanisms involved in angiogenesis, cancer development, and biology and for pharmacological testing of, for example, chemotherapeutic drugs or inhibitors of neoangiogenesis. Moreover, they are useful for studying multicellular responses in toxicology and radiation biology, or for performing coculture experiments. The future will show whether these tissue-engineered constructs can be used for medical transplantations. Unveiling the mechanisms of microgravity-dependent molecular and cellular changes is an up-to-date requirement for improving Space medicine and developing new treatment strategies that can be translated to in vivo models while reducing the use of laboratory animals.

show abstract

How and why does the proteome respond to microgravity?

Cited by 58 publications

References 97 publications

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

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

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

Contact Info

Product

Resources

About