GLUTAMINE IS ESSENTIAL FOR EPIDERMAL GROWTH-FACTOR STIMULATED INTESTINAL-CELL PROLIFERATION

Background. Glutamine stimulates growth of intestinal mucosa in vivo, but the mechanisms involved are unknown. The purpose of this study was to determine whether glutamine is essential for proliferation of ente rocytes stimulated by epidermal growth factor (EGF), In addition, we d etermined which specific mitogenic actions of EGF require glutamine. M ethods. A nontransformed rat intestinal mucosal cell line (IEC-6) was stimulated with EGF (20 ng/ml) without and with glutamine (0.1 to 10 m mol/L). DNA, RNA, and protein synthesis were quantitated by determinin g incorporation of tritiated thymidine, tritiated uridine, and C-14-le ucine, respectively. Cell numbers and messenger RNA levels of early gr owth response genes (zif268, jun-B, c-myc) were also determined. Resul ts. Glutamine was required for EGF stimulation of DNA, RNA, and protei n synthesis and cell replication; however, EGF-stimulated expression o f zif268, jun-B, and c-myc occurred in the absence of glutamine. Concl usions. This study showed that glutamine is essential for EGF-stimulat ed intestinal mucosal cell proliferation. The mitogenic effects of EGF can be divided into the glutamine-independent, such as the signal tra nsduction pathway leading to the induction of early growth response ge nes, and the glutamine-dependent, including DNA, RNA, and protein synt hesis.