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Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes
A Sundaresan1, D Risin, N R Pellis
1Division of Space Life Sciences, Universities Space Research Association, National Aeornautics and Space Administration, Lydon B. Johnson Space Center, Houston, TX 77058-3696, USA. alamelu.sundaresan1@jsc.nasa.gov
Journal of Applied Physiology (Bethesda, Md. : 1985)
|February 18, 2004
Summary
Space travel's microgravity impairs immune cell function by affecting T cell activation and locomotion. Downregulation of specific protein kinase C (PKC) isoforms in lymphocytes may explain these immune system hazards.
Area of Science:
- Immunology
- Space Medicine
- Cellular Biology
Background:
- Long-term space travel exposes astronauts to microgravity and radiation, posing risks to the immune system.
- T cell activation is crucial for immune response, but is inhibited by microgravity.
Purpose of the Study:
- To investigate the effects of modeled microgravity (MMG) on T cell activation and locomotion.
- To identify specific protein kinase C (PKC) isoforms affected by MMG and their role in immune cell function.
Main Methods:
- Lymphocytes were cultured in 1g and MMG conditions for up to 96 hours.
- Lymphocyte locomotion was assessed using type I collagen.
- Expression of PKC isoforms (alpha, delta, epsilon) was analyzed via RT-PCR, flow cytometry, and immunoblotting.
Main Results:
- MMG inhibited lymphocyte activation and locomotion, which could be rescued by direct PKC activation.
- PKC isoforms delta and epsilon were significantly downregulated (>50%) at both transcriptional and translational levels in MMG.
- An upstream signaling defect was observed, with inactive phospholipase Cgamma accumulating in MMG.
Conclusions:
- Downregulation of calcium-independent PKC isoforms (delta, epsilon) in MMG contributes to impaired lymphocyte locomotion.
- The observed immune system impairment may stem from an upstream lesion in the signal transduction pathway affecting PKC activation.