Clinorotation differentially inhibits T-lymphocyte transcription factor activation.
T lymphocytes cultured under the low-shear stress environment of modeled microgravity demonstrate an inhibition of activation in response to T-cell receptor (TCR)-mediated signaling. Modeled microgravity culture-induced inhibition mimics the inhibition observed during spaceflight. This work investigates the molecular signaling events of interleukin 2 transcription activation in modeled microgravity as generated with clinorotation. Under normal conditions, NFAT (nuclear factor of activated T cells) is dephosphorylated and activated with sustained calcium (Ca++) influx and calcineurin activity, whereas AP-1 is activated by protein kinase C (PKC) and Ras-mediated pathways. Purified human T lymphocytes are shown to exhibit differential inhibition of transcription factor activation in modeled microgravity. Activation of AP-1 is blocked with clinorotation, whereas NFAT dephosphorylation occurs. This work supports the theory that modeled microgravity differentially blocks the activation of distinct signaling mechanism.
Morrow
Maureen A
MA
Department of Biology, State University of New York, New Paltz, 75 South Manheim Boulevard, New Paltz, NY 12561-2499, USA. morrowm@newpaltz.edu
D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012399:Rotation; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D018474:Weightlessness Simulation
D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; D018808:Transcription Factor AP-1; D019703:Calcineurin; D002118:Calcium