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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK065345-02
Application #
6795392
Study Section
Special Emphasis Panel (ZRG1-F10 (21))
Program Officer
Podskalny, Judith M,
Project Start
2003-09-01
Project End
2005-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Evans, Mary E; Jones, Dean P; Ziegler, Thomas R (2005) Glutamine inhibits cytokine-induced apoptosis in human colonic epithelial cells via the pyrimidine pathway. Am J Physiol Gastrointest Liver Physiol 289:G388-96
Evans, Mary E; Tian, Junqiang; Gu, Li H et al. (2005) Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats. JPEN J Parenter Enteral Nutr 29:315-20; discussion 320-1
Kucharzik, T; Hudson 3rd, J T; Lugering, A et al. (2005) Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury. Gut 54:1565-72
Alteheld, B; Evans, M E; Gu, L H et al. (2005) Alanylglutamine dipeptide and growth hormone maintain PepT1-mediated transport in oxidatively stressed Caco-2 cells. J Nutr 135:19-26