Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat)

^a University of Alabama in Huntsville, Microgravity Biotechnology Laboratory, Huntsville, Alabama 35899, USA
^b INSERM U311, Establissement de Transfusion Sanguine de Strasbourg, 67065 Strasbourg Cedex, France
^c The Rockefeller University, Steinman-Cohn Laboratory New York, New York 10021, USA
^d Department of Pharmaceutics, University of Texas, Austin, Texas 78235, USA

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.—Lewis, M. L., Reynolds, J. L., Cubano, L. A., Hatton, J. P., Lawless, B. D., Piepmeier, E. H. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J. 12, 1007–1018 (1998)

Key Words: cytoskeleton • Fas/APO-1 • glucose metabolism • MTOC

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