Stimulation of DNA Polymerase α by Hypergravity Generated by Centrifugal Acceleration

Takemura, Masaharu; Yoshida, Shonen

doi:10.1006/bbrc.2001.5986

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…In the present study, a cell centrifuger was used to generate HG conditions and a clinostat was used to generate SMG conditions [40-43], both of which have been widely used to investigate the effects of different gravity conditions on tissue and cell functions during ground-based investigations [27,44]. The cell vessels in the clinostat were horizontally rotated and those in the centrifuger were vertically rotated.…”

Section: Discussionmentioning

confidence: 99%

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Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells

et al. 2009

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BackgroundStem cell therapy has emerged as a potential therapeutic option for tissue engineering and regenerative medicine, but many issues remain to be resolved, such as the amount of seed cells, committed differentiation and the efficiency. Several previous studies have focused on the study of chemical inducement microenvironments. In the present study, we investigated the effects of gravity on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into force-sensitive or force-insensitive cells.Methods and resultsRat BMSCs (rBMSCs) were cultured under hypergravity or simulated microgravity (SMG) conditions with or without inducement medium. The expression levels of the characteristic proteins were measured and analyzed using immunocytochemical, RT-PCR and Western-blot analyses. After treatment with 5-azacytidine and hypergravity, rBMSCs expressed more characteristic proteins of cardiomyocytes such as cTnT, GATA4 and β-MHC; however, fewer such proteins were seen with SMG. After treating rBMSCs with osteogenic inducer and hypergravity, there were marked increases in the expression levels of ColIA1, Cbfa1 and ALP. Reverse results were obtained with SMG. rBMSCs treated with adipogenic inducer and SMG expressed greater levels of PPARgamma. Greater levels of Cbfa1- or cTnT-positive cells were observed under hypergravity without inducer, as shown by FACS analysis. These results indicate that hypergravity induces differentiation of rBMSCs into force-sensitive cells (cardiomyocytes and osteoblasts), whereas SMG induces force-insensitive cells (adipocytes).ConclusionTaken together, we conclude that gravity is an important factor affecting the differentiation of rBMSCs; this provides a new avenue for mechanistic studies of stem cell differentiation and a new approach to obtain more committed differentiated or undifferentiated cells.

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Section: Discussionmentioning

confidence: 99%

“…Kostenuik [50] demonstrated that hindlimb suspension for 5 days significantly decreased the proliferation of BMSCs. Takemura [51] reported that HG increases the activity of DNA polymerase, which may lead to increased cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells

et al. 2009

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“…Gravity alteration (micro-and hypergravity) is known to affect cell morphology, proliferation, response to growth factors, gene expression, and metabolism (1)(2)(3)(4)(5)(6). Recent studies reported that there may be an increased incidence of cancer including melanoma among airline pilots, which could be associated with the exposure to UV radiation and/or to the gravitational alteration (7,8).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Cyclic GMP Efflux in Human Melanocytes by Hypergravity Generated by Centrifugal Acceleration

Ivanova

Zadeh

Block

et al. 2004

Pigment Cell Research

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Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) plays an important role in human melanocyte functions and different guanylyl cyclase isoforms are responsible for cGMP synthesis in human non-metastatic and metastatic melanoma cells, we investigated the effects of hypergravity on the regulation of cGMP levels in cultured human melanocytes and in melanoma cell lines with different metastatic potentials. Hypergravity was produced by horizontal centrifugal acceleration. Here we report that long-term application of hypergravity (up to 5 g for 24 h) stimulated cGMP efflux in cultured melanocytes and in non-metastatic melanoma cells in the presence of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX), a non-selective phosphodiesterase (PDE) inhibitor. Under these conditions, cAMP synthesis and melanin production were up-regulated in pigmented melanocytes and non-metastatic melanoma cells. Hypergravity also stimulated cGMP transport in the presence of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport. Transport was further inhibited by probenecid, an inhibitor of endogenous non-selective transporters as well as of MRP4/5 and by cycloheximide as an inhibitor of de novo protein synthesis. In contrast, hypergravity did not affect cGMP efflux in metastatic melanoma cells, which might be related to an up-regulated cGMP efflux at 1 g. The results of the present study indicate that hypergravity may stimulate cGMP efflux in melanocytes and in non-metastatic melanoma cells most probably by an enhanced expression of endogenous transporters and/or MRP4/5. Thus, an altered acceleration vector may induce signaling events in melanocytic cells.

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“…Glucose consumption at 10 g is reduced with respect to 1 g, whereas the proliferation rate is enhanced. Hypergravity-induced enhancement of proliferation can be related to DNA polymerase α, which is crucial in eukayotic replication, and shows increased activity by stimulation up to 4 g for 1 h (Takemura and Yoshida, 2001). This result may prove particularly useful to the in vitro expansion of stem cells prior to commitment and following implantation in regenerative medicine protocols.…”

Section: Other Bio-molecular Processesmentioning

confidence: 99%

Hypergravity As a Tool for Cell Stimulation: Implications in Biomedicine

Genchi

Rocca

Marino

et al. 2016

Front. Astron. Space Sci.

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Gravity deeply influences numerous biological events in living organisms. Variations in gravity values induce adaptive reactions that have been shown to play important roles, for instance in cell survival, growth, and spatial organization. In this paper, we summarize effects of gravity values higher than that one experienced by cells and tissues on Earth, i.e., hypergravity, with particular attention to the nervous and the musculoskeletal systems. Besides the biological consequences that hypergravity induces in the living matter, we will discuss the possibility of exploiting this augmented force in tissue engineering and regenerative medicine, and thus hypergravity significance as a new therapeutic approach both in vitro and in vivo.

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Stimulation of DNA Polymerase α by Hypergravity Generated by Centrifugal Acceleration

Cited by 6 publications

References 23 publications

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells

Gravity, a regulation factor in the differentiation of rat bone marrow mesenchymal stem cells

Stimulation of Cyclic GMP Efflux in Human Melanocytes by Hypergravity Generated by Centrifugal Acceleration

Hypergravity As a Tool for Cell Stimulation: Implications in Biomedicine

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