Expression of Hypoxia-Inducible Factor 1α (HIF-1α) and Genes of Related Pathways in Altered Gravity

Vogel, Johannes; Thiel, Cora S.; Tauber, Svantje; Stockmann, Christian; Gassmann, Max; Ullrich, Oliver

doi:10.3390/ijms20020436

Cited by 28 publications

(37 citation statements)

References 87 publications

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“…The expression of osteogenic markers such as Runx2 and OCN were also decreased and these results confirmed that dexamethasone could repress the ability and function of osteoblasts. Recent reports have shown that HIF-1α could regulate PDK1 to mediate metabolic effects in different types of cells (15,27). Therefore, we examined PDK1 expression by western blotting.…”

Section: Downregulation Of Hif-1α and Pdk1 By Dexamethasonementioning

confidence: 98%

HIF-1α Regulates Glucocorticoid-Induced Osteoporosis Through PDK1/AKT/mTOR Signaling Pathway

Zheng

Yang

et al. 2020

Front. Endocrinol.

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Long-term and high dose glucocorticoid treatment can cause decreased viability and function of osteoblasts, which leads to osteoporosis and osteonecrosis. In this study, we investigated the role and mechanism of action of HIF-1α in glucocorticoid-induced osteogenic inhibition in MC3T3-E1 cells. Our results showed that HIF-1α protein expression was reduced when MC3T3-E1 cells were exposed to dexamethasone (Dex) at varying concentrations ranging from 10 −9 to 10 −6 M. PDK1 expression was also decreased in MC3T3-E1 cells after dexamethasone treatment. MC3T3-E1 cells when treated with the glucocorticoid receptor antagonist RU486 along with dexamethasone showed enhanced HIF-1α expression. In addition, upregulated expression of HIF-1α was capable of promoting the osteogenic ability of MC3T3-E1 cells and PDK1 expression. However, the HIF-1α antagonist 2-methoxyestradiol (2-ME) had a reverse effect in MC3T3-E1 cells exposed to dexamethasone. Furthermore, the PDK1 antagonist dichloroacetate could repress the osteogenic ability of MC3T3-E1 cells, although HIF-1α was upregulated when transduced with adenovirus-HIF-1α construct. The PDK1 agonist PS48 was able to promote the osteogenic ability of MC3T3-E1 cells treated with dexamethasone. Importantly, the protein levels of p-AKT and p-mTOR were increased in MC3T3-E1 cells treated with dexamethasone after PS48 treatment. in vivo, the PDK1 agonist PS48 could maintain the bone mass of mice treated with dexamethasone. This study provides a new understanding of the mechanism of glucocorticoid-induced osteoporosis.

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Section: Downregulation Of Hif-1α and Pdk1 By Dexamethasonementioning

confidence: 98%

HIF-1α Regulates Glucocorticoid-Induced Osteoporosis Through PDK1/AKT/mTOR Signaling Pathway

Zheng

Yang

et al. 2020

Front. Endocrinol.

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“…The TEXUS-51 mission procedures have been previously described [13,14,55,56]. Briefly, three syringes were assembled into one unit.…”

Section: Texus-51 Mission Proceduresmentioning

confidence: 99%

“…Human Jurkat T cell culture was performed as previously described [13,14,55,56] in the ESRANGE Space Center laboratory facilities. Briefly, sterile plastic syringes were filled with 0.5 mL Jurkat cells (25 million cells).…”

Section: Experimental Preparation Procedures For Texus-51 Experimentsmentioning

confidence: 99%

“…A detailed protocol has been published previously [13,14,55,56]. In summary, the total sample volume of 1.8 mL was sheared three times by passing through a 20 G needle (B. Braun Melsungen, Melsungen, Germany).…”

Section: Rna Purificationmentioning

confidence: 99%

“…A detailed description of RNA sample processing and microarray data analysis can be found in previous publications [13,14,55,56]. Briefly, the Affymetrix GeneChip™ Human Transcriptome Array 2.0 (Affymetrix United Kingdom Ltd., High Wycombe, UK) was used (44,699 protein coding and 22,829 non-protein coding genes).…”

Section: Rna Sample Processing and Microarray Data Analysismentioning

confidence: 99%

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Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation

Thiel

Christoffel

Tauber

et al. 2020

IJMS

Self Cite

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Cellular processes are influenced in many ways by changes in gravitational force. In previous studies, we were able to demonstrate, in various cellular systems and research platforms that reactions and adaptation processes occur very rapidly after the onset of altered gravity. In this study we systematically compared differentially expressed gene transcript clusters (TCs) in human Jurkat T cells in microgravity provided by a suborbital ballistic rocket with vector-averaged gravity (vag) provided by a 2D clinostat. Additionally, we included 9× g centrifuge experiments and rigorous controls for excluding other factors of influence than gravity. We found that 11 TCs were significantly altered in 5 min of flight-induced and vector-averaged gravity. Among the annotated clusters were G3BP1, KPNB1, NUDT3, SFT2D2, and POMK. Our results revealed that less than 1% of all examined TCs show the same response in vag and flight-induced microgravity, while 38% of differentially regulated TCs identified during the hypergravity phase of the suborbital ballistic rocket flight could be verified with a 9× g ground centrifuge. In the 2D clinostat system, doing one full rotation per second, vector effects of the gravitational force are only nullified if the sensing mechanism requires 1 s or longer. Due to the fact that vag with an integration period of 1 s was not able to reproduce the results obtained in flight-induced microgravity, we conclude that the initial trigger of gene expression response to microgravity requires less than 1 s reaction time. Additionally, we discovered extensive gene expression differences caused by simple handling of the cell suspension in control experiments, which underlines the need for rigorous standardization regarding mechanical forces during cell culture experiments in general.

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Neurofluids—Deep inspiration, cilia and preloading of the astrocytic network

Ludwig

Dreha-Kulaczewski

Bock

2021

J of Neuroscience Research

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With the advent of real‐time MRI, the motion and passage of cerebrospinal fluid can be visualized without gating and exclusion of low‐frequency waves. This imaging modality gives insights into low‐volume, rapidly oscillating cardiac‐driven movement as well as sustained, high‐volume, slowly oscillating inspiration‐driven movement. Inspiration means a spontaneous or artificial increase in the intrathoracic dimensions independent of body position. Alterations in thoracic diameter enable the thoracic and spinal epidural venous compartments to be emptied and filled, producing an upward surge of cerebrospinal fluid inside the spine during inspiration; this surge counterbalances the downward pooling of venous blood toward the heart. Real‐time MRI, as a macroscale in vivo observation method, could expand our knowledge of neurofluid dynamics, including how astrocytic fluid preloading is adjusted and how brain buoyancy and turgor are maintained in different postures and zero gravity. Along with these macroscale findings, new microscale insights into aquaporin‐mediated fluid transfer, its sensing by cilia, and its tuning by nitric oxide will be reviewed. By incorporating clinical knowledge spanning several disciplines, certain disorders—congenital hydrocephalus with Chiari malformation, idiopathic intracranial hypertension, and adult idiopathic hydrocephalus—are interpreted and reviewed according to current concepts, from the basics of the interrelated systems to their pathology.

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Expression of Hypoxia-Inducible Factor 1α (HIF-1α) and Genes of Related Pathways in Altered Gravity

Cited by 28 publications

References 87 publications

HIF-1α Regulates Glucocorticoid-Induced Osteoporosis Through PDK1/AKT/mTOR Signaling Pathway

HIF-1α Regulates Glucocorticoid-Induced Osteoporosis Through PDK1/AKT/mTOR Signaling Pathway

Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation

Neurofluids—Deep inspiration, cilia and preloading of the astrocytic network

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