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 enterocytes stimulated by epidermal growth factor (EGF). In addition, we determined which specific mitogenic actions of EGF require glutamine.

METHODS

A nontransformed rat intestinal mucosal cell line (IEC-6) was stimulated with EGF (20 ng/ml) without and with glutamine (0.1 to 10 mmol/L). DNA, RNA, and protein synthesis were quantitated by determining incorporation of tritiated thymidine, tritiated uridine, and 14C-leucine, respectively. Cell numbers and messenger RNA levels of early growth response genes (zif268, jun-B, c-myc) were also determined.

RESULTS

Glutamine was required for EGF stimulation of DNA, RNA, and protein synthesis and cell replication; however, EGF-stimulated expression of zif268, jun-B, and c-myc occurred in the absence of glutamine.

CONCLUSIONS

This study showed that glutamine is essential for EGF-stimulated intestinal mucosal cell proliferation. The mitogenic effects of EGF can be divided into the glutamine-independent, such as the signal transduction pathway leading to the induction of early growth response genes, and the glutamine-dependent, including DNA, RNA, and protein synthesis.