Ko T C, Beauchamp R D, Townsend C M, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston 77555-0533.
Surgery. 1993 Aug;114(2):147-53; discussion 153-4.
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.
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.
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.
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.
谷氨酰胺可在体内刺激肠黏膜生长，但其涉及的机制尚不清楚。本研究的目的是确定谷氨酰胺对于表皮生长因子（EGF）刺激的肠上皮细胞增殖是否必不可少。此外，我们还确定了EGF的哪些特定促有丝分裂作用需要谷氨酰胺。
用EGF（20 ng/ml）刺激未转化的大鼠肠黏膜细胞系（IEC-6），分别在无谷氨酰胺和添加谷氨酰胺（0.1至10 mmol/L）的情况下进行。通过分别测定氚标记胸腺嘧啶核苷、氚标记尿苷和14C-亮氨酸的掺入量来定量DNA、RNA和蛋白质的合成。还测定了细胞数量以及早期生长反应基因（zif268、jun-B、c-myc）的信使RNA水平。
EGF刺激DNA、RNA和蛋白质合成以及细胞复制需要谷氨酰胺；然而，在无谷氨酰胺的情况下，EGF刺激的zif268、jun-B和c-myc的表达仍会发生。
本研究表明，谷氨酰胺对于EGF刺激的肠黏膜细胞增殖至关重要。EGF的促有丝分裂作用可分为不依赖谷氨酰胺的，如导致早期生长反应基因诱导的信号转导途径，以及依赖谷氨酰胺的，包括DNA、RNA和蛋白质合成。
