Effect of Simulated Microgravity on Receptor Mediated Signal Transduction in Hind Limb Suspended Animal Model

Abstract

Microgravity is an extreme environment that affects cellular processes. However, changes in receptor mediated signal transduction processes under such an environment have not been well understood. In this study, we have used a NASA validated Hind Limb Suspension (HLS) model to induce weightlessness in rats and mice and examined any changes in molecules that constitute receptor mediated signal transduction pathways. Animals were hind limb suspended by tail for 21 days. The body weight, food and water intake was monitored. At term, tissue samples were harvested in 20 mM PBS, pH 7.4 and processed for biochemical analyses. Western blots using specific antibodies to alpha subunits of stimulatory (Gs), inhibitory (Gi-1/2) and Gq, a G-protein that couples activation of phosphatidylinositol specific phospholipase C to produce inositol (1,4,5) trisphosphate, showed an increased amounts of Gs, Gi and Gq -proteins in lung, liver, kidney and heart samples of HLS animals as compared to controls. Further, Gq mediated production of inositol phosphates was measured following labeling of rat lung tissues with 3[H]-myo-inositol and analysis by anion exchange chromatography. Results suggested an increased accumulation of total inositol phosphates in HLS animals than in controls. In conclusion, microgravity may affect signaling molecules that mediate cellular signal transduction processes. (Supported by Arkansas Space Grant Consortium, Grant No. UALR-14210).