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Effect of Activation and Regulation of PKC Isoforms in Monocytes under Simulated Microgravity.  C-F. Li, J. P. Hatton, and M. Hughes-Fulford, Lab of Cell Growth, UCSF, NCIRE, and VAMC, San Francisco, CA.

   Early space flight experiments have shown that microgravity suppresses the immune response in humans, including in monocytes.  Protein Kinase C (PKC) is the key protein to control growth and differentiation of monocytes into macrophages.  Studies by Hatton have shown that the distribution, cellular quantity and kinetics of translocation of PKC are altered in microgravity.  In preparation for our Soyuz experiment, we have conducted ground studies of the activation of the PKC using phorbol 12,13-dibutyrate (PDBu) under normal and altered gravity.  We have found a loss of activation of PKC under simulated microgravity.  We then further investigated the gravity sensitivities of the bII, e, and d isoforms and found that both the bII and e isoforms have gravity response component.  Finally, we investigated the gene expression downstream of PKC under normal and altered gravity 3 hours after activation and found that induction of TNFa, ICAM1, IL1b and cox-2 are all significantly reduced under altered gravity.  Expression of these key genes for differentiation of monocytes suggests that signal transduction for activation and differentiation of monocytes are altered in simulated microgravity. These results suggest that gravity is essential for activation of PKC.

(Supported by NASA NCC 2-1361)