Fas/APO-1 protein is increased in spaceflown lymphocytes (Jurkat)☆

Cubano, Luis A.; Lewis, Marian L.

doi:10.1016/s0531-5565(00)00090-5

Cited by 42 publications

(30 citation statements)

References 38 publications

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“…We noted visual differences in nuclear shape in cells growth in mg. Since changes in autocrine, growth, cytoskeletal, and transcription factors may be important in osteoblast physiology in spaceflight [Cubano and Lewis, 2000;Goodwin et al, 2000], we analyzed 24 osteoblast genes under mg, 1 g, and gr conditions. Of the genes with significantly altered expression, there were four cell cycle related, one osteoblast specific, two immediate early, and two growth factor genes reduced at one or both of the timepoints.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that cell growth and differentiation of osteoblasts is inhibited or altered in a microgravity environment [Fitzgerald and Hughes-Fulford, 1996;Hughes-Fulford and Lewis, 1996;Carmeliet et al, 1998;Landis et al, 2000;Granet et al, 2001] suggesting that the osteoporosis seen in spaceflight is occurring at the cellular level. Altered gene expression, reduction in transcription factors, and reductions in growth factor related proteins have also been observed in other cells in microgravity [de Groot et al, 1990;Cubano and Lewis, 2000;Goodwin et al, 2000]. In 2001, Lewis et al found a 5.9-fold reduction in message for TGFa in space-flown lymphocytes [Lewis et al, 2001].…”

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confidence: 94%

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Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity

Hughes‐Fulford

Rodenacker

Jütting

2006

J of Cellular Biochemistry

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Bone loss has been repeatedly documented in astronauts after flight, yet little is known about the mechanism of bone loss in space flight. Osteoblasts were activated during space flight in microgravity (microg) with and without a 1 gravity (1 g) field and 24 genes were analyzed for early induction. Induction of proliferating cell nuclear antigen (PCNA), transforming growth factor beta (TGFbeta), cyclo-oxygenase-2 (cox-2), cpla2, osteocalcin (OC), c-myc, fibroblast growth factor-2 (fgf-2), bcl2, bax, and fgf-2 message as well as FGF-2 protein were significantly depressed in microg when compared to ground (gr). Artificial onboard gravity normalized the induction of c-myc, cox-2, TGFbeta, bax, bcl2, and fgf-2 message as well as FGF-2 protein synthesis in spaceflight samples. In normal gravity, FGF-2 induces bcl2 expression; we found that bcl2 expression was significantly reduced in microgravity conditions. Since nuclear shape is known to elongate in the absence of mitogens like FGF-2, we used high-resolution image-based morphometry to characterize changes in osteoblast nuclear architecture under microgravity, 1 g flight, and ground conditions. Besides changes in cell shape (roundish/elliptic), other high-resolution analyses show clear influences of gravity on the inner nuclear structure. These changes occur in the texture, arrangement, and contrast of nuclear particles and mathematical modeling defines the single cell classification of the osteoblasts. Changes in nuclear structure were evident as early as 24 h after exposure to microgravity. This documented alteration in nuclear architecture may be a direct result of decreased expression of autocrine and cell cycle genes, suggesting an inhibition of anabolic response in microg. Life on this planet has evolved in a normal gravity field and these data suggest that gravity plays a significant role in regulation of osteoblast transcription.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity

Hughes‐Fulford

Rodenacker

Jütting

2006

J of Cellular Biochemistry

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“…20,21 In rat osteoblasts, coinduction of GTP cyclohydrolase I and inducible NO synthase occurred in spaceflight conditions. 22 The stresses associated with spaceflight, including launch vibration, hyper-gravity during launch and landing, experimentallyinduced stresses, and effects of the microgravity environment per se, have been correlated with alterations in the cytoskeleton and microtubule networks, and mitochondrial abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint and physiological apoptosis in germ cells proceeds normally in spaceflown Caenorhabditis elegans

et al. 2005

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It is important for human life in space to study the effects of environmental factors during spaceflight on a number of physiological phenomena. Apoptosis plays important roles in development and tissue homeostasis in metazoans. In this study, we have analyzed apoptotic activity in germ cells of the nematode C. elegans, following spaceflight. Comparison of the number of cell corpses in wild type or ced-1 mutants, grown under either ground or spaceflight conditions, showed that both pachytene-checkpoint apoptosis and physiological apoptosis in germ cells occurred normally under spaceflight conditions. In addition, the expression levels of the checkpoint and apoptosis related genes are comparable between spaceflight and ground conditions. This is the first report documenting the occurrence of checkpoint apoptosis in the space environment and suggests that metazoans, including humans, would be able to eliminate cells that have failed to repair DNA lesions introduced by cosmic radiation during spaceflight.

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“…Various studies report conflicting data on the induction of apoptosis in cells incubated in reduced gravity. In Jurkat cells, apoptosis increased during space flight compared to cells cultured on the ground (12). Many studies on the biological effects of reduced gravity obtained on Earth have modeled microgravity using the clinostat or the Rotating Wall Vessel bioreactor (RWV, Synthecon).…”

Section: Introductionmentioning

confidence: 99%

“Modeled Microgravity” Affects Cell Response to Ionizing Radiation and Increases Genomic Damage

et al. 2005

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The aim of this work was to assess whether "modeled microgravity" affects cell response to ionizing radiation, increasing the risk associated with radiation exposure. Lymphoblastoid TK6 cells were irradiated with various doses of gamma rays and incubated for 24 h in a modeled microgravity environment obtained by the Rotating Wall Vessel bioreactor. Cell survival, induction of apoptosis and cell cycle alteration were compared in cells irradiated and then incubated in 1g or modeled microgravity conditions. Modulation of genomic damage induced by ionizing radiation was evaluated on the basis of HPRT mutant frequency and the micronucleus assay. A significant reduction in apoptotic cells was observed in cells incubated in modeled microgravity after gamma irradiation compared with cells maintained in 1g. Moreover, in irradiated cells, fewer G2-phase cells were found in modeled microgravity than in 1g, whereas more G1-phase cells were observed in modeled microgravity than in 1g. Genomic damage induced by ionizing radiation, i.e. frequency of HPRT mutants and micronucleated cells, increased more in cultures incubated in modeled microgravity than in 1g. Our results indicate that modeled microgravity incubation after irradiation affects cell response to ionizing radiation, reducing the level of radiation-induced apoptosis. As a consequence, modeled microgravity increases the frequency of damaged cells that survive after irradiation.

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Fas/APO-1 protein is increased in spaceflown lymphocytes (Jurkat)☆

Cited by 42 publications

References 38 publications

Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity

Reduction of anabolic signals and alteration of osteoblast nuclear morphology in microgravity

Checkpoint and physiological apoptosis in germ cells proceeds normally in spaceflown Caenorhabditis elegans

“Modeled Microgravity” Affects Cell Response to Ionizing Radiation and Increases Genomic Damage

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