Alteration in cytoskeletal organization appears to underlie mechanisms of gravity sensitivity in space-flown cells. Human T lymphoblastoid cells (Jurkat) were flown on the Space Shuttle to test the hypothesis that growth responsiveness is associated with microtubule anomalies and mediated by apoptosis. Cell growth was stimulated in microgravity by increasing serum concentration. After 4 and 48 h, cells filtered from medium were fixed with formalin. Post-flight, confocal microscopy revealed diffuse, shortened microtubules extending from poorly defined microtubule organizing centers (MTOCs). In comparable ground controls, discrete microtubule filaments radiated from organized MTOCs and branched toward the cell membrane. At 4 h, 30% of flown, compared to 17% of ground, cells showed DNA condensation characteristic of apoptosis. Time-dependent increase of the apoptosis-associated Fas/ APO-1 protein in static flown, but not the in-flight 1 g centrifuged or ground controls, confirmed microgravity-associated apoptosis. By 48 h, ground cultures had increased by 40%. Flown populations did not increase, though some cells were cycling and actively metabolizing glucose. We conclude that cytoskeletal alteration, growth retardation, and metabolic changes in space-flown lymphocytes are concomitant with increased apoptosis and time-dependent elevation of Fas/APO-1 protein. We suggest that reduced growth response in lymphocytes during spaceflight is linked to apoptosis.

Cytoskeletal disruption and growth arrest consistently occur in space‐flown human acute leukemic T cells (Jurkat). Although the microtubules appear to reorganize during spaceflight, cells remain nonproliferative. To test the hypothesis that spaceflight alters cytoskeletal gene expression and may thus affect cytoskeletal function, we flew Jurkat cells on Space Transportation System (STS) 95 and compared RNA message by cDNA microarray in space‐flown vs. ground controls at 24 h (4,324 genes) and 48 h (>20,000 genes). Messages for 11 cytoskeleton‐related genes, including calponin, dynactin, tropomodulin, keratin 8, two myosins, an ankyrin EST, an actinlike protein, the cytoskeletal linker (plectin), and a centriole‐associated protein (C‐NAP1), were up‐regulated in space‐flown compared with ground control cells; gelsolin precursor was down‐regulated. Up‐regulation of plectin and C‐NAP1 message in both space‐flown cells and vibrated controls is a novel finding and implies their role in vibration damage repair. This first report of cDNA microarray screening of gene expression in space‐flown leukemic T cells also identifies differential expression of genes that regulate growth, metabolism, signal transduction, adhesion, transcription, apoptosis, and tumor suppression. Based on differential expression of cytoskeletal genes, we conclude that centriole‐centriole, membrane‐cytoskeletal, and cytoskeletal filament associations are altered in the orbital phase of spaceflight.

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