L-glutamine stimulates intestinal cell proliferation and activates mitogen activated protein kinases. Rhoads, J. Marc, Robert A. Argenzio, Wunian Chen, Richard A. Rippe, John K. Westwick, Adrienne D. Cox, Helen M. Berschneider, and David A. Brenner. Departments of Pediatrics, Medicine, and Radiation Oncology University of North Carolina; the North Carolina State University College of Veterinary Medicine Department of Anatomy, Physiology, and Radiological Sciences; and Center in Gastrointestinal Biology & Disease, Chapel Hill and Raleigh, NC.
APStracts 3:0241G, 1996.
We studied the mechanisms by which L-glutamine (GLN), a major fuel for enterocytes, signals proliferation in intestinal epithelial cell lines. GLN was additive to epidermal growth factor (EGF) and insulin -like growth factor-1 (IGF-1) in stimulating DNA synthesis, as assessed by 3H-thymidine incorporation. Extracellular signal regulated kinases (ERKs) p42mapk and p44mapk and Jun nuclear kinases (JNKs) phosphorylate and activate nuclear transcription factors. Proteins of the c-Jun, ATF-2, and c-Fos families aggregate to form DNA-binding homo- or heterodimers called activating protein-1 (AP-1). In vitro assays and functional assays of phosphorylation demonstrated that GLN activates both ERKs and JNKs, resulting in 4-fold increase in AP-1-dependent gene transcription. GLN was required for EGF signaling through ERKs. Maximal stimulation of proliferation required 2.5 mM GLN. c-Jun mRNA levels responded to GLN in GLN -"starved" porcine IPEC-J2 cells and in rat IEC-6 cells. While GLN metabolism is required for the proliferative response, several GLN by-products did not stimulate 3H-thymidine incorporation, with the exception of arginine. GLN may be a unique nutrient for enterocytes, capable of dual signaling and augmenting the effects of growth factors which govern cellular proliferation and repair. 

Received 26 March 1996; accepted in final form 23 October 1996.
APS Manuscript Number G114-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996