Simulated microgravity triggers DNA damage and mitochondria-mediated apoptosis through ROS generation in human promyelocytic leukemic cells

Singh, Ram; Rajput, Mohit; Singh, Rana P.

doi:10.1016/j.mito.2021.09.006

Cited by 32 publications

(21 citation statements)

References 59 publications

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“…SELENON, a protective component against oxidative stress, was upregulated in the present study, suggesting the involvement of oxidative stress in SMG, as previously reported [ 11 , 25 , 26 ].…”

Section: Discussionsupporting

confidence: 90%

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Montagna

Pani

Flinkman

et al. 2022

Cell. Mol. Life Sci.

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Microgravity-induced bone loss is a major concern for space travelers. Ground-based microgravity simulators are crucial to study the effect of microgravity exposure on biological systems and to address the limitations posed by restricted access to real space. In this work, for the first time, we adopt a multidisciplinary approach to characterize the morphological, biochemical, and molecular changes underlying the response of human bone marrow stromal cells to long-term simulated microgravity exposure during osteogenic differentiation. Our results show that osteogenic differentiation is reduced while energy metabolism is promoted. We found novel proteins were dysregulated under simulated microgravity, including CSC1-like protein, involved in the mechanotransduction of pressure signals, and PTPN11, SLC44A1 and MME which are involved in osteoblast differentiation pathways and which may become the focus of future translational projects. The investigation of cell proteome highlighted how simulated microgravity affects a relatively low number of proteins compared to time and/or osteogenic factors and has allowed us to reconstruct a hypothetical pipeline for cell response to simulated microgravity. Further investigation focused on the application of nanomaterials may help to increase understanding of how to treat or minimize the effects of microgravity.

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Section: Discussionsupporting

confidence: 90%

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Montagna

Pani

Flinkman

et al. 2022

Cell. Mol. Life Sci.

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“…Proliferative processes (also enriching the PI3K/AKT/mTOR pathway [23]) were reduced at 8 days, followed by an upregulation at 28 days of other DAPGs involved in proliferation and speci cally osteoblast proliferation pathways, suggesting changes outcomes for BMSCs. SELENON, a protective component against oxidative stress, was upregulated in the present study, suggesting the involvement of oxidative stress in SMG, as previously reported [11,24,25].…”

Section: Discussionsupporting

confidence: 91%

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Montagna

Pani

Flinkman

et al. 2022

Preprint

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Microgravity induced bone loss is a major concern for space travellers. Ground-based microgravity simulators are crucial to study the effect of microgravity exposure on biological systems and to address the limitations posed by restricted access to real space. In this work, for the first time we adopt a multidisciplinary approach to characterize the morphological, biochemical, and molecular changes underlying the response of human bone marrow stromal cells to long-term simulated microgravity exposure during osteogenic differentiation. Our results show that osteogenic differentiation is reduced while energy metabolism is promoted. We found novel proteins were dysregulated under simulated microgravity, including CSC1-like protein, involved in the mechanotransduction of pressure signals, and PTPN11, SLC44A1 and MME which are involved in osteoblast differentiation pathways and which may become the focus of future translational projects. The investigation of cell proteome highlighted how simulated microgravity affects a relatively low number of proteins compared to time and/or osteogenic factors and has allowed us to reconstruct a hypothetical pipeline for cell response to simulated microgravity. Further investigation focused on the application of nanomaterials may help to increase understanding of how to treat or minimalise the effects of microgravity.

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“…Microgravity has been shown to induce DNA damage and impair DNA damage repair in a variety of cells and conditions [15,[56][57][58][59]. We investigated whether this phenomenon can be observed in T cells in both 2D and 3D cell culture settings.…”

Section: Irregular Nuclear Morphology On T Cells Cultured In 2d Setti...mentioning

confidence: 99%

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

ElGindi

Sapudom

Laws

et al. 2022

Cell. Mol. Life Sci.

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Human space travel and exploration are of interest to both the industrial and scientific community.However, there are many adverse effects of spaceflight on human physiology. In particular, there is a lack of understanding to the extent by which microgravity affects the immune system. T cells, key players of the adaptive immune system and long term immunity, are present not only in blood circulation, but also reside within tissue. As of yet, studies investigating the effects of microgravity on T cells are limited to peripheral blood or traditional 2D cell culture that recapitulates circulating blood. To better mimic interstitial tissue, 3D cell culture has been well established for physiologically and pathologically relevant models. In this work, we utilize 2D and 3D cell culture to gain an understanding of how simulated microgravity affects both circulating and tissue resident T cells. T cells were studied in both resting and activated stages. We found that 3D cell culture attenuates the effects of simulated microgravity on the T cells transcriptome and nuclear irregularities compared to 2D cell culture. Interestingly, simulated microgravity appears to have less effect on activated T cells compared to those in the resting stage. Overall, our work provides novel insights into the effects of simulated microgravity on circulating and tissue resident T cells which could provide benefits for the health of space travelers.

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Simulated microgravity triggers DNA damage and mitochondria-mediated apoptosis through ROS generation in human promyelocytic leukemic cells

Cited by 32 publications

References 59 publications

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

Long-term osteogenic differentiation of human bone marrow stromal cells in simulated microgravity: novel proteins sighted

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

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