Glutamine (GLN) enhances gut mucosal cell proliferation and function during catabolic states. In cultured intestinal cells, GLN deprivation inhibits proliferation and induces apoptosis. The purpose of this research will be to determine the mechanisms behind GLN-induced proliferation and inhibition of apoptosis in intestinal cells. Specifically, this research will examine GLN's ability to prevent apoptosis induced by tumor necrosis factor-alpha related apoptosis-inducing ligand (TRAIL) in human colonic HT-29 cells via both mitochondrial-dependent and mitochondrial-independent pathways. Secondly, this research will investigate the mechanisms underlying the synergistic effect of GLN plus gut-trophic growth factors (e.g. epidermal growth factor) on intestinal cell proliferation. Since GLN serves as a precursor for glutathione (a potent, endogenously-produced antioxidant), redox status and ROS production in GLN-induced proliferation and anti-apoptosis will be examined. Finally, the effect of GLN treatment on Caco-2 epithelial ionic transport and barrier function in cytokine-treated cells under different redox conditions will be examined using electrophysiological methods.
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